Autophagic secretion of mitochondria (ASM): an alternative way for getting rid of damaged mitochondria

ABSTRACTPINK1-PRKN/Parkin-mediated mitophagy represents an important mitochondrial quality control (MQC) pathway that clears damaged/dysfunctional mitochondria. Although the conjugation of mammalian Atg8-family proteins (mATG8s) to phosphatidylethanolamine (PE) is a defining step in autophagy, its role in mitophagy remains unclear. In our recent study, we found that the mATG8 conjugation system is not required for PINK1-PRKN-mediated mitochondria clearance. Instead, mATG8 conjugation system-independent mitochondria clearance relies on secretory autophagy, a process we term as the autophagic secretion of mitochondria (ASM). As ASM results in the spurious activation of the CGAS-STING1 pathway, we propose that defects in mATG8 lipidation may promote inflammation through ASM.KEYWORDS: Extracellular vesiclesinflammationmATG8 conjugation systemmitochondrial quality controlmitophagyPINK1-PRKNsecretory autophagy Disclosure statementNo potential conflict of interest was reported by the authors.Additional informationFundingThis work was supported by the Macau Science and Technology Development Fund [FDCT0078/2020/A2, 0031/2021/A1], Singapore National Medical Research Council grant [NMRC/CIRG/1490/201] and Ministry of Education grant[MOE2018-T2-1-060] awarded to H.M.S.