ATG5: A central autophagy regulator implicated in various human diseases

Abstract

Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy‐independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy‐dependent and autophagy‐independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target.

Validation of mitophagy mechanism within steroid-induced osteonecrosis of the femoral head by bioinformatics analysis and experiments

“…OPTN is an autophagy receptor that is associated with many human diseases closely related to autophagy, such as rheumatoid arthritis, osteoporosis and nephropathy 33 . ATG5, a classical autophagic core protein, is essential in autophagic expression 34 , and experimental ndings by zhu 35 and others found that ATG5 knockdown attenuated autophagy-induced iron death. SOD1 is an anti-oxidant metalloenzyme catalyzing the dissociation of superoxide anion radicals to produce oxygen and hydrogen superoxide.…”

Sirt1 ameliorated cardiac autophagic flux blockage via Prx2 during myocardial ischemia/reperfusion injury

“…Lamp2 is associated with the lysosomal membrane, and the reduction of Lamp2 will lead to lysosomal dysfunction [30]. Autophagyrelated gene 5 (Atg5), essential for autophagic vesicle formation and autophagosomes maturation, has also been proven to be a regulator of autophagic ux [31]. Compared with the Ad.GFP + NC + H 2 O 2 group, overexpression of Sirt1 alone could increase autolysosomes by increased expressions of Rab7 and Lamp2, rather than Atg5.…”

Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

“…The ATG12–ATG5–ATG16L conjugate plays a role in both binding and closure processes, it was found that ATG12 was catalyzed by ATG7 to bind to ATG5. This conjugate then interacts with other autophagy associated proteins, primarily ATG8, to form complexes that regulate autophagy protein formation (Changotra et al, 2022). The closure process, which represents the formation of a complete two‐membrane autophagosome, is the process by which the phagosome will need to be completely surrounded by the isolated material.…”