View source for Lysosome

{{short description|Cell membrane organelle}}
{{Distinguish|Lysozyme|lectins}}
{{Use dmy dates|date=August 2017}}
{{Organelle diagram}}
A '''lysosome''' ({{IPA|en|ˈlaɪsəˌsoʊm}}) is a membrane-bound [[organelle]] that is found in all [[animal cell]]s, (except [[red blood cell]]s), and rarely in [[plant cell]]s.<ref name="libre2025">{{cite web |title=4.8B: Lysosomes |url=https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/04%3A_Cell_Structure_of_Bacteria_Archaea_and_Eukaryotes/4.08%3A_Other_Eukaryotic_Components/4.8B%3A_Lysosomes |website=Biology LibreTexts |access-date=6 November 2025 |language=en |date=8 May 2017}}</ref> There are normally hundreds of lysosomes in the [[cytosol]], where they function as the cell's degradation center. Their primary responsibility is catabolic degradation of proteins, polysaccharides and lipids into their respective building-block molecules: amino acids, monosaccharides, and free fatty acids. The breakdown is done by various enzymes, for example proteases, glycosidases and lipases.<ref name=hx>{{cite journal |last1=Xu |first1=Haoxing |last2=Ren |first2=Dejian |title=Lysosomal Physiology |journal=Annual Review of Physiology |date=10 February 2015 |volume=77 |issue=1 |pages=57–80 |doi=10.1146/annurev-physiol-021014-071649 |pmc=4524569 |pmid=25668017 }}</ref>

With an acidic lumen limited by a single-bilayer lipid membrane, the lysosome holds an environment isolated from the rest of the cell. The lower pH creates optimal conditions for the over 60 different [[Hydrolase|hydrolases]] inside.<ref name="Settembre-2013">{{cite journal |last1=Settembre |first1=Carmine |last2=Fraldi |first2=Alessandro |last3=Medina |first3=Diego L. |last4=Ballabio |first4=Andrea |title=Signals from the lysosome: a control centre for cellular clearance and energy metabolism |journal=Nature Reviews Molecular Cell Biology |date=May 2013 |volume=14 |issue=5 |pages=283–296 |doi=10.1038/nrm3565 |pmc=4387238 |pmid=23609508 }}</ref>

Lysosomes receive extracellular particles through [[endocytosis]], and intracellular components through [[autophagy]].<ref name=hx/> They can also fuse with the plasma membrane and secrete their contents, a process called lysosomal [[exocytosis]].<ref name="Settembre-2013" /> After degradation lysosomal products are transported out of the lysosome through specific membrane proteins or via vesicular membrane trafficking to be recycled or to be utilized for energy.<ref name=hx/>

Aside from cellular clearance and secretion, lysosomes mediate biological processes like plasma membrane repair, cell [[homeostasis]], energy metabolism, cell signaling, and the immune response.<ref name="Settembre-2013" />

==Discovery==
[[File:Christian de Duve.tif|thumb|Christian de Duve, age 95, presenting his ideas on the origin of the eukaryotic cell (October 2012)]]
[[Christian de Duve]], a Belgian scientist at the Laboratory of Physiological Chemistry at the [[Université Catholique de Louvain|Catholic University of Louvain]], is credited with discovering lysosomes in the 1950s. De Duve and his team were studying the distribution of hydrolytic enzymes such as [[acid phosphatase]] within cells, using [[cell fractionation]] methods to isolate subcellular components. De Duve and his team identified an unknown organelle that was rich in acid phosphatase. This led them to propose the existence of lysosomes as membrane bound organelles containing digestive enzymes capable of breaking down a variety of biological molecules.

Using [[differential centrifugation]] and enzyme activity assays, the team confirmed the hypothesis and understood that these organelles play a crucial role in intracellular digestion processes, such as [[phagocytosis]] and [[autophagy]]. The presence of digestive enzymes was further validated using electron microscopy. De Duve's discovery laid the foundation for new research into lysosomal functions and understanding disorders which could lead to undigested materials accumulating in the cell. De Duve was awarded the [[Nobel Prize in Physiology or Medicine]] in 1974.<ref name="Sabatini Adesnik Christian de Duve">{{cite journal |last1=Sabatini |first1=David D. |last2=Adesnik |first2=Milton |title=Christian de Duve: Explorer of the cell who discovered new organelles by using a centrifuge |journal=Proceedings of the National Academy of Sciences |date=13 August 2013 |volume=110 |issue=33 |pages=13234–13235 |doi=10.1073/pnas.1312084110 |doi-access=free |pmc=3746853 |pmid=23924611 |bibcode=2013PNAS..11013234S }}</ref><ref>{{cite book |last1=Cooper |first1=Geoffrey M. |title=The Cell: A Molecular Approach |edition=2nd |date=2000 |publisher=Sinauer Associates |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK9953/ |chapter=Lysosomes }}</ref>

== Function and structure ==
[[File:The Biological bulletin (19756543133).jpg|thumb|TEM views of various vesicular compartments. Lysosomes are denoted by "Ly". They are dyed dark due to their acidity; in the center of the top image, a Golgi Apparatus can be seen, distal from the cell membrane relative to the lysosome.]]
Lysosomes vary in shape and size depending on their state, what they are digesting, and the cell type they are in.<ref name="Kühnel-2003">{{Cite book |last1=Kühnel |first1=Wolfgang |title=Color atlas of cytology, histology, and microscopic anatomy |last2=Kühnel |first2=Wolfgang |date=2003 |publisher=Thieme |isbn=978-1-58890-175-0 |edition=4th |series=Thieme Flexibook Basic sciences |location=Stuttgart New York}}{{pn|date=April 2025}}</ref> Their shape can differ from spherical and ovoid to occasionally tubular.<ref name="Bouhamdani A Compendium of Information on the Lysosome">{{cite journal |last1=Bouhamdani |first1=Nadia |last2=Comeau |first2=Dominique |last3=Turcotte |first3=Sandra |title=A Compendium of Information on the Lysosome |journal=Frontiers in Cell and Developmental Biology |date=15 December 2021 |volume=9 |article-number=798262 |doi=10.3389/fcell.2021.798262 |doi-access=free |pmc=8714965 |pmid=34977038 }}</ref> The size of lysosomes ranges from 0.1-1.2 μm,<ref name="Kühnel-2003" /> with some tubular ones reaching up to 15 μm in [[phagocyte]]s. Several hundred lysosomes can be found within a single cell. However, upon nutrient deprivation or induced autophagy, their numbers can drop below 50 in a cell.<ref name="Bouhamdani A Compendium of Information on the Lysosome"/>

Lysosomes contain a variety of enzymes that enable the cell to break down various biomolecules it engulfs, including [[Peptide|peptides]], [[Nucleic acid|nucleic acids]], [[Carbohydrate|carbohydrates]], and [[Lipid|lipids]]. The enzymes responsible for this hydrolysis require an acidic environment for optimal activity, with a pH ranging from ~4.5–5.0. The interior of the lysosome is acidic compared to the slightly basic cytosol (pH 7.2).<ref>{{cite journal |last1=Feng |first1=Xinghua |last2=Liu |first2=Siyu |last3=Xu |first3=Haoxing |title=Not just protons: Chloride also activates lysosomal acidic hydrolases |journal=Journal of Cell Biology |date=5 June 2023 |volume=222 |issue=6 |article-number=e202305007 |doi=10.1083/jcb.202305007 |pmc=10191866 |pmid=37191899 }}</ref>

The lysosomal membrane is a phospholipid bilayer with high carbohydrate content from heavily glycosylated membrane proteins. This forms a [[glycocalyx]] that protects the cell from the [[Degradative enzyme|degradative enzymes]] held within the lysosome. Lysosomal hydrolases are pH-sensitive and do not function properly in the alkaline environment of the cytosol, ensuring that molecules and organelles in the cytosol are not degraded if there is leakage of hydrolytic enzymes from the lysosome.

In addition to breaking down polymers, lysosomes are capable of killing and digesting microbes, cells, or cellular debris. Through cooperation with [[Phagosome|phagosomes]], lysosomes conduct [[autophagy]], clearing out damaged structures and forming simple compounds, which are then used as new building materials. Similarly, lysosomes break down virus particles or bacteria during phagocytosis in macrophages.<ref>{{cite news |last1=Brouillette |first1=Monique |title=Biology 101 Update: A Cell's Lysosomes Are More Than Garbage Disposals |url=https://www.scientificamerican.com/article/biology-101-update-a-cell-rsquo-s-lysosomes-are-more-than-garbage-disposals/ |work=Scientific American |date=1 December 2016 }}</ref>

Lysosomes also help detect pathogens through [[Toll-like receptor|toll-like receptors]] (TLRs), like TLR7 and TLR9. Microbes can be degraded into antigens, which are then loaded onto MHC molecules and presented to T-cells, a critical part of immune defense. Additionally, lysosomal enzymes can trigger lysosomal-mediated programmed cell death (LM-PCD) if released into the cytoplasm.

To maintain their acidic environment, lysosomes pump protons (H⁺ ions) from the cytosol into the lysosomal lumen via a proton pump in the lysosomal membrane. [[V-ATPase|Vacuolar-ATPases]] are responsible for the transport of protons, while the counter transport of chloride ions is performed by ClC-7 Cl⁻/H⁺ antiporter.<ref>{{cite journal |last1=Feng |first1=Xinghua |last2=Liu |first2=Siyu |last3=Xu |first3=Haoxing |title=Not just protons: Chloride also activates lysosomal acidic hydrolases |journal=Journal of Cell Biology |date=5 June 2023 |volume=222 |issue=6 |article-number=e202305007 |doi=10.1083/jcb.202305007 |pmc=10191866 |pmid=37191899 }}</ref> This mechanism helps maintain a steady acidic environment, as well as ionic homeostasis, within the lysosome.<ref>{{cite journal |last1=Mindell |first1=Joseph A. |title=Lysosomal Acidification Mechanisms |journal=Annual Review of Physiology |date=17 March 2012 |volume=74 |issue=1 |pages=69–86 |doi=10.1146/annurev-physiol-012110-142317 |pmid=22335796 }}</ref><ref>{{cite journal |last1=Ishida |first1=Yoichi |last2=Nayak |first2=Smita |last3=Mindell |first3=Joseph A. |last4=Grabe |first4=Michael |title=A model of lysosomal pH regulation |journal=Journal of General Physiology |date=June 2013 |volume=141 |issue=6 |pages=705–720 |doi=10.1085/jgp.201210930 |pmc=3664703 |pmid=23712550 }}</ref>

Lysosomes also help balance cellular metabolism by sensing nutrient availability. When nutrients are plentiful, they activate [[MTOR signaling pathway|mTOR signaling]] to support anabolic (biosynthetic) processes. During starvation, lysosomes degrade autophagic material, recycling components to maintain cell survival.

== Lysosomal degradation pathways ==
[[File:Lysosomes as catabolic centers of the cell.jpg|thumb|399x399px|Cellular material is delivered to lysosomes in four different ways; (A) Macroautophagy, (B) Endosomal degradation, (C) Microautophagy and (D) Chaperone-mediated autophagy (CMA).]]
The lysosome is delivered material for degradation via transient interactions or complete fusion, forming endolysosomes and autolysosomes respectively. This way, the lysosomes act as reservoirs for acidic hydrolases, cycling through fusion and fission events with late endosomes and autophagosomes. The actual breakdown of endocytic and autophagic cargo primarily happens within these transient structures—endolysosomes and autolysosomes—under normal physiological conditions.<ref name="Platt Lysosomal storage disorders"/>

Endocytosed materials – such as complex lipids, membrane proteins, and polysaccharides – enter the endocytic pathway; moving first in early endosomes, then in late endosomes containing intraluminal vesicles (also referred to as multivesicular bodies, MVBs). Then they interact with lysosomes, either via full fusion, or via "kiss-and-run" events where brief membrane contact allows content exchange before the organelles separate. The resulting hybrid structure is called an endolysosome.<ref name="Samie Xu Lysosomal exocytosis">{{cite journal |last1=Samie |first1=Mohammad Ali |last2=Xu |first2=Haoxing |title=Lysosomal exocytosis and lipid storage disorders |journal=Journal of Lipid Research |date=June 2014 |volume=55 |issue=6 |pages=995–1009 |doi=10.1194/jlr.R046896 |doi-access=free |pmc=4031951 |pmid=24668941 }}</ref><ref name="Platt Lysosomal storage disorders"/>

Intracellular materials – like damaged organelles or misfolded proteins – are processed through the autophagic pathway.<ref name="Samie Xu Lysosomal exocytosis"/> Autophagy, or "self-eating," is a continuous cellular process that delivers cytosolic components to lysosomes for degradation. There are three main types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)—each differing in how cargo is delivered to the lysosome.<ref name="Platt Lysosomal storage disorders"/> After merging with lysosomes they create hybrid organelles called autolysosomes.<ref name="Samie Xu Lysosomal exocytosis"/>

* Macroautophagy involves the formation of isolated double- or multi-membranes that encapsulate portions of cytosolic material such as misfolded- or polyubiquitinated proteins, lipids, damaged or aged organelles, RNA, and fragments of the ER. These vesicles mature into autophagosomes and then fuse with lysosomes for degradation, creating an autolysosome. A key marker of autophagosomes is LC3-II, a lipidated form of microtubule-associated protein light chain 3 (MAP-LC3) that appears early in the process and is broken down during digestion
* Microautophagy bypasses vesicle formation altogether, with lysosomes directly engulfing surrounding cytosolic material through membrane invagination; pinocytosis. This process is similar to the formation of intraluminal vesicles in MVBs.
* Chaperone-mediated autophagy (CMA) selectively degrades proteins that contain a KFERQ motif. These substrates are recognized by Hsc70, which binds them and delivers them to lysosomes via the receptor LAMP-2A for degradation.<ref name="Platt Lysosomal storage disorders"/>


The resulting catabolites serve as building-block molecules for synthesizing complex macromolecules. These are exported from lysosomes via specific transporters or through vesicle trafficking. Once released into the cytosol or delivered to the Golgi apparatus, these catabolites are either further metabolized to generate energy or reused in biosynthetic pathways to form new complex molecules. Alternatively, some degradation products can be secreted out of the lysosomes through exocytosis.<ref name="Samie Xu Lysosomal exocytosis"/>

Because catabolic (degradative) and anabolic (biosynthetic) pathways are interconnected and tightly regulated, the flow of cargo through the endocytic and autophagic systems is modulated by cellular signaling and nutrient availability. Nutrient deprivation, for example, activates autophagy, which is then halted once lysosomal degradation is complete. Lysosomes themselves play a direct role in sensing nutrient levels through the lysosomal nutrient-sensing (LYNUS) system, which includes components such as V-ATPase, Rag GTPases, and the mTOR complex.<ref name="Samie Xu Lysosomal exocytosis"/>

== Formation ==
[[File:Phagocytosis.svg|alt=|thumb|Process of phagocytosis: 1. A particle is ingested by a [[phagocyte]] after antigens are recognized which results in the formation of a [[phagosome]]. 2. The fusion of lysosomes with the phagosome creates a [[phagolysosome]]. The particle is broken down by the digestive enzymes found in the lysosomes.]]
The formation of lysosomes begins in the endoplasmic reticulum, where hydrolytic enzymes are synthesized. These enzymes are then transported to the Golgi apparatus (Golgi body), where they undergo modifications to ensure proper targeting and function. The enzymes are tagged with mannose-6-phosphate,<ref name="Coutinho Mannose-6-phosphate pathway">{{cite journal |last1=Coutinho |first1=Maria Francisca |last2=Prata |first2=Maria João |last3=Alves |first3=Sandra |title=Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction |journal=Molecular Genetics and Metabolism |date=April 2012 |volume=105 |issue=4 |pages=542–550 |doi=10.1016/j.ymgme.2011.12.012 |pmid=22266136 }}</ref> allowing them to be sorted into vesicles. These vesicles then bud off from the trans-Golgi network and fuse with early endosomes.<ref name="Coutinho Mannose-6-phosphate pathway"/><ref>{{cite journal |last1=Luzio |first1=J. P. |last2=Hackmann |first2=Y. |last3=Dieckmann |first3=N. M. G. |last4=Griffiths |first4=G. M. |title=The Biogenesis of Lysosomes and Lysosome-Related Organelles |journal=Cold Spring Harbor Perspectives in Biology |date=September 2014 |volume=6 |issue=9 |article-number=a016840 |doi=10.1101/cshperspect.a016840 |pmc=4142962 |pmid=25183830 }}</ref>

Early endosomes degrade cargo from the extracellular environment, and as they mature into late endosomes, proton pumps are activated, causing the internal environment to become acidic. This acidic environment activates the hydrolytic enzymes, which further mature the endosome into a lysosome.<ref>{{cite journal |last1=Nguyen |first1=Jenny A. |last2=Yates |first2=Robin M. |title=Better Together: Current Insights Into Phagosome-Lysosome Fusion |journal=Frontiers in Immunology |date=25 February 2021 |volume=12 |article-number=636078 |doi=10.3389/fimmu.2021.636078 |doi-access=free |pmc=7946854 |pmid=33717183 }}</ref> The lysosome then breaks down and recycles cellular waste.<ref name="Kaur Early Endosome Morphology">{{cite book |last1=Kaur |first1=Gulpreet |last2=Lakkaraju |first2=Aparna |chapter=Early Endosome Morphology in Health and Disease |title=Retinal Degenerative Diseases |series=Advances in Experimental Medicine and Biology |date=2018 |volume=1074 |pages=335–343 |doi=10.1007/978-3-319-75402-4_41 |pmc=6563932 |pmid=29721961 |isbn=978-3-319-75401-7 }}</ref>

Disruptions in lysosomal formation can lead to dysfunctional lysosomes and the accumulation of undigested molecules, contributing to various lysosomal storage disorders.<ref name="Kaur Early Endosome Morphology"/>

== Pathogen entry ==
Lysosomes are a crucial component of the [[innate immune system]] and play an important role in defending the cell against pathogens such as viruses or bacteria. When a pathogen enters the cell, it is often enclosed in a [[phagosome]], which then fuses with a lysosome to form a [[phagolysosome]] where the hydrolytic enzymes break down the pathogen.<ref name="Bird Edgington-Mitchell Newton Eat, prey, love">{{cite journal |last1=Bird |first1=Lauren E |last2=Edgington-Mitchell |first2=Laura E |last3=Newton |first3=Hayley J |title=Eat, prey, love: Pathogen-mediated subversion of lysosomal biology |journal=Current Opinion in Immunology |date=August 2023 |volume=83 |article-number=102344 |doi=10.1016/j.coi.2023.102344 |pmid=37245414 }}</ref><ref name="Sabatini Adesnik Christian de Duve"/> 

Lysosomes also play a big role in the [[adaptive immune system]]. Fragments of pathogens that have been broken down by phagolysosomes are sent to the major histocompatibility complex class II (MHC II) and presented on the surface of antigen presenting cells (APCs). This then activates helper T cells, which causes an adaptive immune response.<ref>{{cite book |title=InformedHealth.org [Internet] |date=14 August 2023 |publisher=Institute for Quality and Efficiency in Health Care (IQWiG) |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK279396/ |chapter=In brief: The innate and adaptive immune systems }}</ref>

Just like other pathogens, viruses entering the cell via endocytosis are degraded in lysosomes. However, some viruses have evolved strategies to escape degradation by lysosomes, and are able to escape the lysosome before complete degradation and spread viral material into the cytoplasm which then spreads viral infection in the cell. Poor lysosomal activity and failure by lysosomes to properly degrade all biomolecules from pathogens results in higher viral infections by viruses such as HIV.<ref name="Sabatini Adesnik Christian de Duve" /><ref>{{cite journal |last1=Wei |first1=Bangdong L. |last2=Denton |first2=Paul W. |last3=O'Neill |first3=Eduardo |last4=Luo |first4=Tianci |last5=Foster |first5=John L. |last6=Garcia |first6=J. Victor |title=Inhibition of Lysosome and Proteasome Function Enhances Human Immunodeficiency Virus Type 1 Infection |journal=Journal of Virology |date=May 2005 |volume=79 |issue=9 |pages=5705–5712 |doi=10.1128/jvi.79.9.5705-5712.2005 |pmc=1082736 |pmid=15827185 }}</ref> 

==Clinical significance==

[[Lysosomal storage disorder]]s are a group of metabolic disorders that stem from inherited genetic mutations that disrupt normal lysosomal function and homeostasis.<ref name="Samie Xu Lysosomal exocytosis"/><ref name="Platt Lysosomal storage disorders">{{cite journal |last1=Platt |first1=Frances M. |last2=Boland |first2=Barry |last3=van der Spoel |first3=Aarnoud C. |title=Lysosomal storage disorders: The cellular impact of lysosomal dysfunction |journal=Journal of Cell Biology |date=26 November 2012 |volume=199 |issue=5 |pages=723–734 |doi=10.1083/jcb.201208152 |pmc=3514785 |pmid=23185029 }}</ref> Most frequently, the mutations are located in the acidic hydrolases, but can also be found in non-enzymatic lysosomal proteins (soluble and membrane-bound) and non-lysosomal factors controlling lysosomal function.<ref>{{Cite journal |last1=Carmona-Gutierrez |first1=Didac |last2=Hughes |first2=Adam L. |last3=Madeo |first3=Frank |last4=Ruckenstuhl |first4=Christoph |date=2016-12-01 |title=The crucial impact of lysosomes in aging and longevity |journal=Ageing Research Reviews |volume=32 |pages=2–12 |doi=10.1016/j.arr.2016.04.009 |pmc=5081277 |pmid=27125853}}</ref> This leads to defective degradation, which induces abnormal accumulations of undigested or partially digested macromolecules within lysosomes. Lysosomal dysfunction also affects transport across the lysosomal membrane, vesicle trafficking, lysosome reformation and autophagy.<ref>{{Cite journal |last1=Bouhamdani |first1=Nadia |last2=Comeau |first2=Dominique |last3=Turcotte |first3=Sandra |date=2021-12-15 |title=A Compendium of Information on the Lysosome |journal=Frontiers in Cell and Developmental Biology |language=English |volume=9 |article-number=798262 |doi=10.3389/fcell.2021.798262 |doi-access=free |pmid=34977038 |pmc=8714965 }}</ref><ref name="Samie Xu Lysosomal exocytosis"/>

The stress of accumulated lysosomal substrates can lead to lysosomal membrane permeabilization, allowing hydrolytic enzymes to leak into the cytosol and initiate cell death. This cell loss particularly affects post-mitotic tissues such as the brain, liver, eyes, muscles, and spleen—resulting in the hallmark symptoms of lysosomal storage disorders, including neurodegeneration, cognitive impairment, and motor dysfunction.<ref name="Platt Lysosomal storage disorders"/><ref>{{Cite journal |last1=Carmona-Gutierrez |first1=Didac |last2=Hughes |first2=Adam L. |last3=Madeo |first3=Frank |last4=Ruckenstuhl |first4=Christoph |date=2016-12-01 |title=The crucial impact of lysosomes in aging and longevity |journal=Ageing Research Reviews |volume=32 |pages=2–12 |doi=10.1016/j.arr.2016.04.009 |pmc=5081277 |pmid=27125853}}</ref>

The age of onset and the specific symptoms in lysosomal storage disorders differ depending on the severity of the mutations, the cell types affected and what substrates accumulate. However, the clinical presentation is typically a neurodegenerative disease at childhood, with more variations presenting themselves in adulthood. In most cases, the central nervous system (CNS) is affected, causing the brain to experience global neurodegeneration, inflammation, activation of the innate immune system and [[astrogliosis]].<ref name="Platt Lysosomal storage disorders"/>

Several therapeutic strategies have been developed to address lysosomal storage disorders. These include substrate reduction therapy, bone marrow transplantation, gene therapy, and enzyme replacement therapy. Currently, enzyme replacement therapy and substrate reduction are the most widely used. However, despite these advancements, most lysosomal storage disorders still lack effective treatments as the existing ones are limited by poor efficacy and are typically disease specific.<ref name="Platt Lysosomal storage disorders"/>

===Lysosomotropism===

Lysosomotropism refers to the tendency of lipophilic weak bases to accumulate in acidic organelles like lysosomes. While neutral forms of these compounds cross membranes easily, their protonated (charged) forms become trapped inside lysosomes, leading to concentrations up to 1000 times higher than outside the cell.<ref>{{cite journal |last1=de Duve |first1=Christian |last2=de Barsy |first2=Thierry |last3=Poole |first3=Brian |last4=Trouet |first4=André |last5=Tulkens |first5=Paul |last6=van Hoof |first6=François |title=Lysosomotropic agents |journal=Biochemical Pharmacology |date=September 1974 |volume=23 |issue=18 |pages=2495–2531 |doi=10.1016/0006-2952(74)90174-9 |pmid=4606365 }}</ref><ref>{{cite book |doi=10.1016/s0091-679x(08)61717-3 |chapter=Chapter 12 Lysosomal Proton Pump Activity: Supravital Cell Staining with Acridine Orange Differentiates Leukocyte Subpopulations |title=Flow Cytometry Second Edition, Part A |series=Methods in Cell Biology |date=1994 |last1=Traganos |first1=Frank |last2=Darzynkiewicz |first2=Zbigniew |volume=41 |pages=185–194 |pmid=7532261 |isbn=978-0-12-564142-5 }}</ref> This "acid trapping" or "proton pump" effect can be predicted using mathematical models.<ref>{{cite journal |last1=Trapp |first1=Stefan |last2=Rosania |first2=Gus R. |last3=Horobin |first3=Richard W. |last4=Kornhuber |first4=Johannes |title=Quantitative modeling of selective lysosomal targeting for drug design |journal=European Biophysics Journal |date=October 2008 |volume=37 |issue=8 |pages=1317–1328 |doi=10.1007/s00249-008-0338-4 |pmc=2711917 |pmid=18504571 }}</ref>

Many approved drugs, including haloperidol,<ref>{{cite journal |last1=Kornhuber |first1=Johannes |last2=Schultz |first2=Andreas |last3=Wiltfang |first3=Jens |last4=Meineke |first4=Ingolf |last5=Gleiter |first5=Christoph H. |last6=Zöchling |first6=Robert |last7=Boissl |first7=Karl-Werner |last8=Leblhuber |first8=Friedrich |last9=Riederer |first9=Peter |title=Persistence of Haloperidol in Human Brain Tissue |journal=American Journal of Psychiatry |date=June 1999 |volume=156 |issue=6 |pages=885–890 |doi=10.1176/ajp.156.6.885 |pmid=10360127 }}</ref> levomepromazine,<ref>{{cite journal |last1=Kornhuber |first1=J. |last2=Weigmann |first2=H. |last3=Röhrich |first3=J. |last4=Wiltfang |first4=J. |last5=Bleich |first5=S. |last6=Meineke |first6=I. |last7=Zöchling |first7=R. |last8=Härtter |first8=S. |last9=Riederer |first9=P. |last10=Hiemke |first10=C. |title=Region specific distribution of levomepromazine in the human brain |journal=Journal of Neural Transmission |date=March 2006 |volume=113 |issue=3 |pages=387–397 |doi=10.1007/s00702-005-0331-3 |pmid=15997416 }}</ref> and amantadine,<ref>{{cite journal |last1=Kornhuber |first1=J. |last2=Quack |first2=G. |last3=Danysz |first3=W. |last4=Jellinger |first4=K. |last5=Danielczyk |first5=W. |last6=Gsell |first6=W. |last7=Riederer |first7=P. |title=Therapeutic brain concentration of the NMDA receptor antagonist amantadine |journal=Neuropharmacology |date=July 1995 |volume=34 |issue=7 |pages=713–721 |doi=10.1016/0028-3908(95)00056-C |pmid=8532138 }}</ref> exhibit lysosomotropic behavior. This helps explain their high tissue-to-blood concentration ratios and prolonged tissue retention, though fat solubility also contributes.

Some lysosomotropic drugs can interfere with lysosomal enzymes like acid sphingomyelinase.<ref>{{cite journal |last1=Kornhuber |first1=Johannes |last2=Tripal |first2=Philipp |last3=Reichel |first3=Martin |last4=Terfloth |first4=Lothar |last5=Bleich |first5=Stefan |last6=Wiltfang |first6=Jens |last7=Gulbins |first7=Erich |title=Identification of New Functional Inhibitors of Acid Sphingomyelinase Using a Structure−Property−Activity Relation Model |journal=Journal of Medicinal Chemistry |date=2008 |volume=51 |issue=2 |pages=219–237 |doi=10.1021/jm070524a |pmid=18027916 }}</ref><ref>{{Cite journal |last1=Kornhuber |first1=Johannes |last2=Muehlbacher |first2=Markus |last3=Trapp |first3=Stefan |last4=Pechmann |first4=Stefanie |last5=Friedl |first5=Astrid |last6=Reichel |first6=Martin |last7=Mühle |first7=Christiane |last8=Terfloth |first8=Lothar |last9=Groemer |first9=Teja W. |last10=Spitzer |first10=Gudrun M. |last11=Liedl |first11=Klaus R. |last12=Gulbins |first12=Erich |last13=Tripal |first13=Philipp |date=2011-08-31 |title=Identification of Novel Functional Inhibitors of Acid Sphingomyelinase |journal=PLOS ONE |volume=6 |issue=8 |article-number=e23852 |doi=10.1371/journal.pone.0023852 |doi-access=free |pmc=3166082 |pmid=21909365 |bibcode=2011PLoSO...623852K }}</ref> Ambroxol, a mucolytic, promotes lysosomal exocytosis by neutralizing lysosomal pH and releasing stored calcium.<ref>{{cite journal |last1=Marshall |first1=Kirsty |last2=Easton |first2=Chris |title=The role of asset-based approaches in community nursing |journal=Primary Health Care |date=25 July 2018 |volume=28 |issue=5 |pages=35–38 |doi=10.7748/phc.2018.e1339 }}</ref> This action may underlie its observed benefits in diseases linked to lysosomal dysfunction, including Parkinson's disease and lysosomal storage disorders.<ref>{{cite journal |last1=Albin |first1=Roger L. |last2=Dauer |first2=William T. |title=Magic shotgun for Parkinson's disease? |journal=Brain |date=May 2014 |volume=137 |issue=5 |pages=1274–1275 |doi=10.1093/brain/awu076 |pmid=24771397 }}</ref><ref>{{Cite journal |last1=McNeill |first1=Alisdair |last2=Magalhaes |first2=Joana |last3=Shen |first3=Chengguo |last4=Chau |first4=Kai-Yin |last5=Hughes |first5=Derralyn |last6=Mehta |first6=Atul |last7=Foltynie |first7=Tom |last8=Cooper |first8=J. Mark |last9=Abramov |first9=Andrey Y. |last10=Gegg |first10=Matthew |last11=Schapira |first11=Anthony H. V. |date=May 2014 |title=Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells |journal=Brain: A Journal of Neurology |volume=137 |issue=Pt 5 |pages=1481–1495 |doi=10.1093/brain/awu020 |pmc=3999713 |pmid=24574503 }}</ref>

=== Systemic lupus erythematosus (Lupus) ===
Systemic lupus erythematosus (SLE) otherwise known as Lupus is an autoimmune disease where the immune system attacks healthy cells.<ref>{{Cite web |date=2025-04-03 |title=Lupus: Symptoms & Treatment |url=https://my.clevelandclinic.org/health/diseases/4875-lupus |access-date=2025-04-09 |archive-url=http://web.archive.org/web/20250403230150/https://my.clevelandclinic.org/health/diseases/4875-lupus |archive-date=3 April 2025 }}</ref> Lupus is prominent in systemic lupus erythematosus preventing macrophages and monocytes from degrading neutrophil extracellular traps<ref>{{Cite journal |last1=Hakkim |first1=Abdul |last2=Fürnrohr |first2=Barbara G. |last3=Amann |first3=Kerstin |last4=Laube |first4=Britta |last5=Abed |first5=Ulrike Abu |last6=Brinkmann |first6=Volker |last7=Herrmann |first7=Martin |last8=Voll |first8=Reinhard E. |last9=Zychlinsky |first9=Arturo |date=2010-05-25 |title=Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis |journal=Proceedings of the National Academy of Sciences |volume=107 |issue=21 |pages=9813–9818 |doi=10.1073/pnas.0909927107 |doi-access=free |pmc=2906830 |pmid=20439745|bibcode=2010PNAS..107.9813H }}</ref> and immune complexes.<ref name="Monteith-2016">{{Cite journal |last1=Monteith |first1=Andrew J. |last2=Kang |first2=SunAh |last3=Scott |first3=Eric |last4=Hillman |first4=Kai |last5=Rajfur |first5=Zenon |last6=Jacobson |first6=Ken |last7=Costello |first7=M. Joseph |last8=Vilen |first8=Barbara J. |date=2016-04-12 |title=Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus |journal=Proceedings of the National Academy of Sciences |volume=113 |issue=15 |pages=E2142–E2151 |doi=10.1073/pnas.1513943113 |doi-access=free |pmc=4839468 |pmid=27035940|bibcode=2016PNAS..113E2142M }}</ref><ref>{{cite journal |last1=Kavai |first1=Maria |last2=Szegedi |first2=Gyula |title=Immune complex clearance by monocytes and macrophages in systemic lupus erythematosus |journal=Autoimmunity Reviews |date=August 2007 |volume=6 |issue=7 |pages=497–502 |doi=10.1016/j.autrev.2007.01.017 |pmid=17643939 }}</ref><ref>{{cite journal |last1=KáVai |first1=M. |last2=Csipö |first2=I. |last3=Sonkoly |first3=J. |last4=Csongor |first4=J. |last5=Szegedi |first5=G. Y. |title=Defective Immune Complex Degradation by Monocytes in Patients with Systemic Lupus Erythematosus. |journal=Scandinavian Journal of Immunology |date=November 1986 |volume=24 |issue=5 |pages=527–532 |doi=10.1111/j.1365-3083.1986.tb02167.x |pmid=3787186 }}</ref> The failure to degrade internalized immune complexes rises from irregularly extended activity of mTORC2, which impairs lysosome acidification.<ref>{{Cite journal |last1=Monteith |first1=Andrew J |last2=Vincent |first2=Heather A |last3=Kang |first3=SunAh |last4=Li |first4=Patrick |last5=Claiborne |first5=Tauris M |last6=Rajfur |first6=Zenon |last7=Jacobson |first7=Ken |last8=Moorman |first8=Nathaniel J |last9=Vilen |first9=Barbara J |date=2018-07-01 |title=mTORC2 Activity Disrupts Lysosome Acidification in Systemic Lupus Erythematosus by Impairing Caspase-1 Cleavage of Rab39a |journal=The Journal of Immunology |volume=201 |issue=2 |pages=371–382 |doi=10.4049/jimmunol.1701712 |pmc=6039264 |pmid=29866702}}</ref> As a result, immune complexes in the lysosome recycle to the surface of macrophages causing an accumulation of DNA fragments and nuclear complexes which triggers an immune response from the body which is leads to the multiple lupus-associated pathologies.<ref name="Monteith-2016" /><ref>{{Cite journal |last1=Kang |first1=SunAh |last2=Rogers |first2=Jennifer L |last3=Monteith |first3=Andrew J |last4=Jiang |first4=Chuancang |last5=Schmitz |first5=John |last6=Clarke |first6=Stephen H |last7=Tarrant |first7=Teresa K |last8=Truong |first8=Young K |last9=Diaz |first9=Marilyn |last10=Fedoriw |first10=Yuri |last11=Vilen |first11=Barbara J |date=2016-05-01 |title=Apoptotic Debris Accumulates on Hematopoietic Cells and Promotes Disease in Murine and Human Systemic Lupus Erythematosus |journal=The Journal of Immunology |volume=196 |issue=10 |pages=4030–4039 |doi=10.4049/jimmunol.1500418 |pmc=4868781 |pmid=27059595}}</ref><ref>{{Cite journal |last1=Kang |first1=SunAh |last2=Fedoriw |first2=Yuri |last3=Brenneman |first3=Ethan K |last4=Truong |first4=Young K |last5=Kikly |first5=Kristine |last6=Vilen |first6=Barbara J |date=2017-04-01 |title=BAFF Induces Tertiary Lymphoid Structures and Positions T Cells within the Glomeruli during Lupus Nephritis |journal=The Journal of Immunology |volume=198 |issue=7 |pages=2602–2611 |doi=10.4049/jimmunol.1600281 |pmc=5360485 |pmid=28235864}}</ref>

== Different types of enzymes present in lysosomes ==

There are over 50 different types of hydrolytic enzymes in lysosomes, the table below shows a few of the main types and their substrates. It is important to keep in mind that each category below has multiple different types of enzymes. 
{| class="wikitable"
|+
!Sr. No
!Enzymes
!Substrate 
|-
|1
|[[Protease|Proteases]]
|Proteins and Peptides (breaks peptide bonds)<ref>{{cite book |doi=10.1016/B978-0-12-378630-2.00063-3 |chapter=Protein Degradation |title=Encyclopedia of Biological Chemistry |date=2013 |last1=Goldberg |first1=A.L. |pages=617–624 |isbn=978-0-12-378631-9 }}</ref>
|-
|2
|[[Nuclease|Nucleases]]
|DNA and RNA (cleaves phosphodiester bonds)<ref>{{cite journal |last1=Cao |first1=Xiangjian |last2=Sun |first2=Ying |last3=Lu |first3=Peng |last4=Zhao |first4=Meiping |title=Fluorescence imaging of intracellular nucleases—A review |journal=Analytica Chimica Acta |date=November 2020 |volume=1137 |pages=225–237 |doi=10.1016/j.aca.2020.08.013 |pmid=33153605 |bibcode=2020AcAC.1137..225C }}</ref>
|-
|3
|[[Glycoside hydrolase|Glycosidases]]
|Carbohydrates (breaks glycosidic bonds)<ref>{{cite book |doi=10.1016/B978-008045382-8.00660-2 |chapter=Enzymatic Synthesis of Complex Carbohydrates |title=Comprehensive Natural Products II |date=2010 |last1=Zhao |first1=Wei |last2=Li |first2=Tiehai |last3=Woodward |first3=Robert |last4=Xia |first4=Chengfeng |last5=Wang |first5=Peng George |last6=Guan |first6=Wanyi |pages=5–54 |isbn=978-0-08-045382-8 }}</ref>
|-
|4
|[[Lipase|Lipases]]
|Lipids (breaks ester bonds)<ref>{{cite book |doi=10.1016/B978-0-323-89929-1.00034-2 |chapter=Enzymes in seafood processing |title=Value-Addition in Food Products and Processing Through Enzyme Technology |date=2022 |last1=Mathew |first1=Gincy Marina |last2=Huang |first2=Chieh Chen |last3=Sindhu |first3=Raveendran |last4=Binod |first4=Parameswaran |last5=Pandey |first5=Ashok |pages=189–204 |isbn=978-0-323-89929-1 }}</ref>
|-
|5
|[[Phospholipase|Phospholipases]]
|Phospholipids (cleaves fatty acids from phospholipids)<ref>{{cite book |doi=10.1016/B978-0-12-800047-2.00002-4 |chapter=The Lipids of Biological Membranes |title=The Membranes of Cells |date=2016 |last1=Yeagle |first1=Philip L. |pages=27–56 |isbn=978-0-12-800047-2 }}</ref>
|-
|7
|[[Phosphatase|Phosphatases]]
|Phosphorylated molecules (removes phosphate groups)<ref>{{cite journal |doi=10.1016/j.freeradbiomed.2019.12.027 |title=Non-redox cycling mechanisms of oxidative stress induced by PM metals |date=2020 |last1=Samet |first1=James M. |last2=Chen |first2=Hao |last3=Pennington |first3=Edward R. |last4=Bromberg |first4=Philip A. |journal=Free Radical Biology and Medicine |volume=151 |pages=26–37 |pmid=31877355 |pmc=7803379 }}</ref>
|-
|8
|[[Sulfatase|Sulfatases]]
|Sulfated molecules (removes sulphate groups)<ref>{{cite book |doi=10.1016/S0076-6879(10)80003-5 |chapter=Use of a Phage Display Antibody to Measure the Enzymatic Activity of the Sulfs |title=Glycobiology |series=Methods in Enzymology |date=2010 |last1=Uchimura |first1=Kenji |last2=Lemjabbar-Alaoui |first2=Hassan |last3=Van Kuppevelt |first3=Toin H. |last4=Rosen |first4=Steven D. |volume=480 |pages=51–64 |pmid=20816204 |isbn=978-0-12-380999-5 }}</ref>
|}

== See also ==
* [[Peroxisome]]
* [[Cathelicidin]]
* [[Antimicrobial peptides]]
* [[Innate immune system]]
* [[TMEM106B]]
* [[Endosome|Endosomes]]

== References ==
<references />

== External links ==
{{wiktionary}}
* {{NCBI-scienceprimer}}
* [http://opm.phar.umich.edu/localization.php?localization=Lysosome%20membrane 3D structures of proteins associated with lysosome membrane]
* [http://www.hideandseek.org Hide and Seek Foundation For Lysosomal Research]
*[http://www.lysosomaldiseasenetwork.org/ Lysosomal Disease Network, a research consortium funded by the NIH through its NCATS/Rare Diseases Clinical Research Network]
* [https://www.nytimes.com/2009/10/06/science/06cell.html Self-Destructive Behavior in Cells May Hold Key to a Longer Life]
* {{cite journal |last1=Kang |first1=Changsoo |last2=Riazuddin |first2=Sheikh |last3=Mundorff |first3=Jennifer |last4=Krasnewich |first4=Donna |last5=Friedman |first5=Penelope |last6=Mullikin |first6=James C. |last7=Drayna |first7=Dennis |title=Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering |journal=New England Journal of Medicine |date=25 February 2010 |volume=362 |issue=8 |pages=677–685 |doi=10.1056/NEJMoa0902630 |pmid=20147709 |pmc=2936507 }}
* [http://highered.mcgraw-hill.com/olc/dl/120067/bio01.swf Animation showing how lysosomes are made, and their function]

{{organelles}}

{{Authority control}}

[[Category:Vesicles]]
[[Category:Cell anatomy]]
[[Category:Cell biology]]
[[Category:Eukaryotic cell anatomy]]
[[Category:Organelles]]
[[Category:Lysosomal storage diseases]]