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{{short description|Cell membrane organelle}}▼
{{Distinguish|Lysozyme|lectins}}
▲{{short description|Cell organelle}}
{{Use dmy dates|date=August 2017}}
{{Organelle diagram}}
A '''
[[File:Lysosomes Digestion.svg|thumb|Lysosomes digest
Lysosomes
In 2009, Marco Sardiello and co-workers discovered that the synthesis of most lysosomal enzymes and membrane proteins is controlled by transcription factor EB ([[TFEB]]), which promotes the transcription of [[nuclear gene]]s.<ref name = "Underwood_2018">{{cite journal|title=When the brain's waste disposal system fails |journal=Knowable Magazine |
==Etymology and pronunciation==
The word ''lysosome'' ({{IPAc-en|ˈ|l|aɪ|s|oʊ|s|oʊ|m}}, {{IPAc-en|ˈ|l|aɪ|z|ə|z|oʊ|m}}) is [[
==Discovery==
[[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 .]]
They succeeded in detecting the enzyme activity from the [[microsome|microsomal]] fraction. This was the crucial step in the serendipitous discovery of lysosomes. To estimate this enzyme activity, they used that of the standardized enzyme [[acid phosphatase]] and found that the activity was only 10% of the expected value. One day, the enzyme activity of purified cell fractions which had been refrigerated for five days was measured. Surprisingly, the enzyme activity was increased to normal of that of the fresh sample. The result was the same no matter how many times they repeated the estimation, and led to the conclusion that a membrane-like barrier limited the accessibility of the enzyme to its substrate, and that the enzymes were able to diffuse after a few days (and react with their substrate). They described this membrane-like barrier as a "saclike structure surrounded by a membrane and containing acid phosphatase."<ref>{{cite journal |author= Susana Castro-Obregon|year= 2010 |title= The Discovery of Lysosomes and Autophagy |url= http://www.nature.com/scitable/topicpage/the-discovery-of-lysosomes-and-autophagy-14199828|journal= Nature Education |volume=3 |issue= 9 | pages=49 }}</ref>
It became clear that this enzyme from the cell fraction came from membranous fractions, which were definitely cell organelles, and in 1955 De Duve named them "lysosomes" to reflect their digestive properties.<ref>{{cite journal | vauthors = de Duve C | title = The lysosome turns fifty | journal = Nature Cell Biology | volume = 7 | issue = 9 | pages =
Originally, De Duve had termed the organelles the "suicide bags" or "suicide sacs" of the cells, for their hypothesized role in [[apoptosis]].<ref>Hayashi, Teru, and others. "Subcellular Particles." ''Subcellular Particles.'', 1959.</ref> However, it has since been concluded that they only play a minor role in [[cell death]].<ref>{{cite journal | vauthors = Turk B, Turk V | year = 2009| title = Lysosomes as 'Suicide Bags' in Cell Death: Myth or Reality? | journal = The Journal of Biological Chemistry | volume = 284 | issue = 33| pages = 21783–87 | doi = 10.1074/jbc.R109.023820 | pmid = 19473965| pmc = 2755904 | doi-access = free}}</ref>▼
▲Originally, De Duve had termed the organelles the "suicide bags" or "suicide sacs" of the cells, for their hypothesized role in [[apoptosis]].<ref>Hayashi, Teru, and others. "Subcellular Particles." ''Subcellular Particles.'', 1959.</ref> However, it has since been concluded that they only play a minor role in [[cell death]].<ref>{{cite journal | vauthors = Turk B, Turk V
== Function and structure ==
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In addition to being able to break down polymers, lysosomes are capable of fusing with other organelles & digesting large structures or cellular debris; through cooperation with [[phagosome]]s, they are able to conduct [[autophagy]], clearing out damaged structures. Similarly, they are able to break down virus particles or bacteria in [[phagocytosis]] of [[macrophage]]s.
The size of lysosomes varies from 0.1 [[micrometre|μm]] to 1.2 [[micrometre|μm]].<ref>{{cite book |
The lysosome maintains its pH differential by pumping in [[proton]]s (H<sup>+</sup> ions) from the cytosol across the [[Cell membrane|membrane]] via [[proton pump]]s and [[chloride channel|chloride ion channel]]s. [[V-ATPase|Vacuolar-ATPase]]s are responsible for transport of protons, while the counter transport of chloride ions is performed by [[CLCN7|ClC-7]] Cl<sup>−</sup>/H<sup>+</sup> antiporter. In this way a steady acidic environment is maintained.<ref name="Lysosomal acidification mechanisms">{{cite journal | vauthors = Mindell JA |
It sources its versatile capacity for degradation by import of enzymes with specificity for different substrates; [[cathepsin]]s are the major class of hydrolytic enzymes, while [[Acid alpha-glucosidase|lysosomal alpha-glucosidase]] is responsible for carbohydrates, and [[ACP2|lysosomal acid phosphatase]] is necessary to release phosphate groups of phospholipids.
Recent research also indicates that lysosomes can act as a source of intracellular calcium.<ref>{{cite journal | vauthors = Medina DL, Di Paola S, Peluso I, Armani A, De Stefani D, Venditti R, Montefusco S, Scotto-Rosato A, Prezioso C, Forrester A, Settembre C, Wang W, Gao Q, Xu H, Sandri M, Rizzuto R, De Matteis MA, Ballabio A | display-authors = 6 | title = Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB | journal = Nature Cell Biology | volume = 17 | issue = 3 | pages = 288–299 | date = March 2015 | pmid = 25720963 | pmc = 4801004 | doi = 10.1038/ncb3114 }}</ref>
== Formation ==
[[File:Endocytic pathway of animal cells showing EGF receptors, transferrin receptors and mannose-6-phosphate receptors.jpg|alt=This is crucial for many disease pathways|thumb|The lysosome is shown in purple, as an endpoint in endocytotic sorting. AP2 is necessary for vesicle formation, whereas the mannose-6-receptor is necessary for sorting hydrolase into the lysosome's lumen.]]
Many components of animal cells are recycled by transferring them inside or embedded in sections of membrane. For instance, in [[endocytosis]] (more specifically, [[macropinocytosis]]), a portion of the cell's plasma membrane pinches off to form vesicles that will eventually fuse with an organelle within the cell. Without active replenishment, the plasma membrane would continuously decrease in size. It is thought that lysosomes participate in this dynamic membrane exchange system and are formed by a gradual maturation process from [[endosomes]].<ref name=Alberts>{{cite book|
The production of lysosomal proteins suggests one method of lysosome sustainment. Lysosomal protein genes are transcribed in the [[Cell nucleus|nucleus]] in a process that is controlled by transcription factor EB ([[TFEB]]).<ref name="pmid19556463"
Upon leaving the Golgi apparatus, the lysosomal enzyme-filled vesicle fuses with a [[Endosome#Types|late endosome]], a relatively acidic organelle with an approximate pH of 5.5. This acidic environment causes dissociation of the lysosomal enzymes from the mannose 6-phosphate receptors. The enzymes are packed into vesicles for further transport to established lysosomes.<ref name=Lodish /> The late endosome itself can eventually grow into a mature lysosome, as evidenced by the transport of endosomal membrane components from the lysosomes back to the endosomes.<ref name=Alberts />
== Pathogen entry ==
As the endpoint of endocytosis, the lysosome also acts as a safeguard in preventing pathogens from being able to reach the cytoplasm before being degraded. Pathogens often hijack endocytotic pathways such as [[pinocytosis]] in order to gain entry into the cell. The lysosome prevents easy entry into the cell by hydrolyzing the biomolecules of pathogens necessary for their replication strategies; reduced
==Clinical significance==
Lysosomes are involved in a group of genetically inherited deficiencies, or mutations called [[lysosomal storage diseases]] (LSD), [[inborn errors of metabolism]] caused by a dysfunction of one of the enzymes. The rate of incidence is estimated to be 1 in 5,000 births, and the true figure expected to be higher as many cases are likely to be undiagnosed or misdiagnosed. The primary cause is deficiency of an [[acid hydrolase]]. Other conditions are due to defects in lysosomal membrane proteins that fail to transport the enzyme, non-enzymatic soluble lysosomal proteins. The initial effect of such disorders is accumulation of specific macromolecules or monomeric compounds inside the endosomal–autophagic–lysosomal system.<ref name=platt/> This results in abnormal signaling pathways, [[calcium homeostasis]], [[Lipid synthesis|lipid biosynthesis]] and degradation and intracellular trafficking, ultimately leading to pathogenetic disorders. The organs most affected are [[Central nervous system|brain]], [[viscera]], bone and [[cartilage]].<ref>{{cite journal | vauthors = Schultz ML, Tecedor L, Chang M, Davidson BL | title = Clarifying lysosomal storage diseases | journal = Trends in Neurosciences | volume = 34 | issue = 8 | pages =
There is no direct medical treatment to cure LSDs.<ref>.{{cite journal | vauthors = Parenti G, Pignata C, Vajro P, Salerno M | title = New strategies for the treatment of lysosomal storage diseases (review) | journal = International Journal of Molecular Medicine | volume = 31 | issue = 1 | pages = 11–20 | date = January 2013 | pmid = 23165354 | doi = 10.3892/ijmm.2012.1187 | doi-access = free }}</ref> The most common LSD is [[Gaucher's disease]], which is due to deficiency of the enzyme [[glucocerebrosidase]]. Consequently, the enzyme substrate, the fatty acid [[glucosylceramide]] accumulates, particularly in [[white blood cells]], which in turn affects spleen, liver, kidneys, lungs, brain and bone marrow. The disease is characterized by bruises, fatigue, [[anaemia]], low blood platelets, [[osteoporosis]], and enlargement of the liver and spleen.<ref>{{cite journal | vauthors = Rosenbloom BE, Weinreb NJ | title = Gaucher disease: a comprehensive review | journal = Critical Reviews in Oncogenesis | volume = 18 | issue = 3 | pages =
The most severe and rarely found, lysosomal storage disease is [[inclusion cell disease]].<ref name="Alberts2004">{{cite book |
[[Metachromatic leukodystrophy]] is another lysosomal storage disease that also affects [[sphingolipid metabolism]].
Dysfunctional lysosome activity is also heavily implicated in the biology of [[Ageing|aging]], and age-related diseases such as Alzheimer's, Parkinson's, and cardiovascular disease.
== Different enzymes present in Lysosomes ==
{| class="wikitable"
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|E- Lysozymes
|Bacterial cell walls and
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===Lysosomotropism===
Weak [[Base (chemistry)|bases]] with [[Lipophilicity|lipophilic]] properties accumulate in acidic intracellular compartments like lysosomes. While the plasma and lysosomal membranes are permeable for neutral and uncharged species of weak bases, the charged protonated species of weak bases do not permeate biomembranes and accumulate within lysosomes. The concentration within lysosomes may reach levels 100 to 1000 fold higher than extracellular concentrations. This phenomenon is called [[wikt:lysosomotropism|lysosomotropism]],<ref>{{cite journal | vauthors = de Duve C, de Barsy T, Poole B, Trouet A, Tulkens P, Van Hoof F | title = Commentary. Lysosomotropic agents | journal = Biochemical Pharmacology | volume = 23 | issue = 18 | pages =
A significant part of the clinically approved drugs are lipophilic weak bases with lysosomotropic properties. This explains a number of pharmacological properties of these drugs, such as high tissue-to-blood concentration gradients or long tissue elimination half-lives; these properties have been found for drugs such as [[haloperidol]],<ref>{{cite journal | vauthors = Kornhuber J, Schultz A, Wiltfang J, Meineke I, Gleiter CH, Zöchling R, Boissl KW, Leblhuber F, Riederer P | display-authors = 6 | title = Persistence of haloperidol in human brain tissue | journal = The American Journal of Psychiatry | volume = 156 | issue = 6 | pages =
[[Ambroxol]] is a lysosomotropic drug of clinical use to treat conditions of productive cough for its mucolytic action. Ambroxol triggers the exocytosis of lysosomes via neutralization of lysosomal pH and [[Calcium channel opener|calcium release]] from acidic calcium stores.<ref>{{cite journal | vauthors = Fois G, Hobi N, Felder E, Ziegler A, Miklavc P, Walther P, Radermacher P, Haller T, Dietl P | display-authors = 6 | title = A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca²⁺ release from acidic Ca²⁺ stores | journal = Cell Calcium | volume = 58 | issue = 6 | pages =
=== Systemic lupus erythematosus ===
Impaired lysosome function is prominent in systemic lupus erythematosus preventing macrophages and monocytes from degrading neutrophil extracellular traps<ref>{{cite journal | vauthors = Hakkim A, Fürnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, Herrmann M, Voll RE, Zychlinsky A | display-authors = 6 | title = Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 21 | pages =
== Controversy in botany ==
By scientific convention, the term lysosome is applied to these vesicular organelles only in animals, and the term [[vacuole]] is applied to those in plants, fungi and algae (some animal cells also have vacuoles). Discoveries in plant cells since the 1970s started to challenge this definition. Plant vacuoles are found to be much more diverse in structure and function than previously thought.<ref>{{cite journal | vauthors = Marty F | title = Plant vacuoles | journal = The Plant Cell | volume = 11 | issue = 4 | pages = 587–600 | date = April 1999 | pmid = 10213780 | pmc = 144210 | doi = 10.2307/3870886 | jstor = 3870886 }}</ref><ref>{{cite journal | vauthors = Samaj J, Read ND, Volkmann D, Menzel D, Baluska F | title = The endocytic network in plants | journal = Trends in Cell Biology | volume = 15 | issue = 8 | pages =
== See also ==
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* [[Antimicrobial peptides]]
* [[Innate immune system]]
* [[TMEM106B]]
== References ==
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[[Category:Vesicles]]
[[Category:Cell anatomy]]
[[Category:Eukaryotic cell anatomy]]
[[Category:Organelles]]
[[Category:Lysosomal storage diseases]]
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