Editing Programmed cell death (section)

=== Autophagy ===

[[Macroautophagy]], often referred to as [[autophagy]], is a [[catabolic]] process that results in the [[Autophagosome|autophagosomic]]-[[Lysosome|lysosomal]] degradation of bulk [[cytoplasm]]ic contents, abnormal protein aggregates, and excess or damaged [[organelle]]s.{{cn|date=November 2024}}

[[Autophagy]] is generally activated by conditions of [[nutrient]] deprivation but has also been associated with [[Physiology|physiolog]]ical as well as [[Pathology|patholog]]ical processes such as development, differentiation, [[neurodegenerative]] [[disease]]s, [[Stress (physiology)|stress]], [[infection]] and [[cancer]].{{cn|date=November 2024}}

==== Mechanism ====

A critical regulator of autophagy induction is the [[kinase]] [[mTOR]], which when activated, suppresses [[autophagy]] and when not activated promotes it. Three related [[serine]]/[[threonine]] kinases, UNC-51-like kinase -1, -2, and -3 (ULK1, ULK2, UKL3), which play a similar role as the yeast [[Atg1]], act downstream of the [[mTOR]] complex. [[ULK1]] and [[ULK2]] form a large complex with the mammalian [[homolog]] of an autophagy-related (Atg) gene product (mAtg13) and the scaffold protein FIP200. Class III PI3K complex, containing hVps34, [[BECN1|Beclin-1]], p150 and Atg14-like protein or ultraviolet irradiation resistance-associated gene (UVRAG), is required for the induction of autophagy.{{cn|date=November 2024}}

The [[Methionine|ATG]] [[gene]]s control the [[autophagosome]] formation through [[ATG12]]-[[ATG5]] and LC3-II ([[ATG8]]-II) complexes. [[ATG12]] is conjugated to [[ATG5]] in a [[ubiquitin]]-like reaction that requires [[ATG7]] and [[ATG10]]. The Atg12–Atg5 conjugate then interacts non-covalently with ATG16 to form a large complex. LC3/[[ATG8]] is cleaved at its C terminus by ATG4 [[protease]] to generate the cytosolic LC3-I. LC3-I is conjugated to phosphatidylethanolamine (PE) also in a ubiquitin-like reaction that requires Atg7 and Atg3. The lipidated form of LC3, known as LC3-II, is attached to the autophagosome membrane.{{cn|date=November 2024}}

[[Autophagy]] and [[apoptosis]] are connected both positively and negatively, and extensive crosstalk exists between the two. During [[Malnutrition|nutrient deficiency]], [[autophagy]] functions as a pro-survival mechanism, however, excessive [[autophagy]] may lead to [[cell death]], a process [[Morphology (biology)|morphologically]] distinct from [[apoptosis]]. Several pro-apoptotic [[Cell signaling|signals]], such as [[TNF]], [[TRAIL]], and [[FADD]], also induce autophagy. Additionally, [[Bcl-2]] inhibits [[BECN1|Beclin-1]]-dependent autophagy, thereby functioning both as a pro-survival and as an anti-autophagic regulator.{{cn|date=November 2024}}