Fig. 1: Mechanism of macromitophagy.
From: Mechanism and role of mitophagy in the development of severe infection
After cells suffer endogenous and exogenous stimulators, mitophagy is initiated to clear injured mitochondria by recruiting PINK1-Parkin to ubiquitinate mitochondria. The ULK1 complex and PI3KC3 complex I synthesize robust PI3P at the omegasome. Autophagy adapters or receptors bind ATG8 to anchor mitochondria to the phagophore. The double membrane of the phagophore lengthens and enwraps mitochondria. Mitophagosomes fuse with lysosomes mediated by the tethering proteins (such as HOPS complex and PLEKHM1) and SNAREs. Finally, lysosomal enzymes degrade the inner membrane and contents of the mitophagosome. Various microorganisms, such as CVB3, IAV, Legionella, HPIV3, SARS-CoV-2, and Hantavirus, disturb the process of mitophagy, resulting in mitochondria injury and autophagosome accumulation. ATG autophagy-related, COP-II coat protein complex-II, CVB3 coxsackievirus B3, ER endoplasmic reticulum, HOPS homotypic fusion and protein sorting, HPIV3 human parainfluenza virus 3, IAV influenza A virus, LPS lipopolysaccharides, PI3P phosphatidylinositol-3-phosphate, PINK1 PTEN-induced putative kinase 1, PLEKHM1 pleckstrin homology domain-containing protein family member 1, RAB7A RAS oncogene family 7A, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor, TBK1 TANK binding kinase 1, TLR toll-like receptor, ULK1 unc-51 like autophagy activating kinase 1, WIPI WD repeat domain phosphoinositide interacting.
