The role of autophagy poses as a highly conserved catabolic phenomena where cells undergoing stress

800 WordsApr 23, 20194 Pages
The role of autophagy poses as a highly conserved catabolic phenomena where cells undergoing stress develop a cytoplasmic crescent shaped phagophore that matures into an autophagosome. The autophagosome is involved in engulfing damaged organelles and long lived proteins in order to replenish the cellular energy content and building blocks for biosynthesis. The autophagy phenomenon always occurs to maintain the cellular homeostasis. But, under stress there is triggering of this autophagy event beyond its basal level. The most important breakthrough in our understanding of the molecular pathway of autophagy came from yeast genetic analysis where 35 Atg (Autophagy-related) genes were identified. Various types of Cellular stress sparks an…show more content…
Ultimately, PI3P plays a crucial localization response to facilitate fusion at the last step of double-membrane autophagosome synthesis. Binding between Vps34 and Beclin-1 is enhanced by Ambra-1 (activating molecule in Beclin1-regulated autophagy protein-1), Bif-1 (Bax interacting factor-1), and UVRAG (ultraviolet radiation resistance-associated gene) whereas Bcl-XL, Bcl-2 and Rubicon (Run domain Beclin-1 interacting cysteine-rich containing protein) inhibits this interaction. Another stress induced transmembrane protein is vacuole membrane protein 1(VMP1) which interacts with Beclin-1 to induce autophagy. A couple of ubiquitin-like conjugation system gets involved during autophagosome elongation through a chain of events. Atg 12 interacts with Atg 7 (E1 ubiquitin-like activating enzyme), following which Atg12 binds to Atg10 (E2-like ubiquitin carrier), thereby linking Atg12 to Atg5; then, Atg16 dimers gets attached to this complex resulting in phagophore expansion. The Atg5-Atg12-Atg16 complex helps in the growth of the nascent edges of the phagophore. This trimeric conjugation drops out when the phagophore finally matures into the autophagosome. A second ubiquitin- like system is involved in microtubule associated protein light chain 3 (LC3, mammalian homolog of yeast Atg8) processing.Atg4 cleaves LC3 to an active intermediate LC3I by conjugating with E1-like Atg7 through an ATP dependent

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