Editing Lysosome (section)

== 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"/>