RRC ID 71885
Author Tan HWS, Lu G, Dong H, Cho YL, Natalia A, Wang L, Chan C, Kappei D, Taneja R, Ling SC, Shao H, Tsai SY, Ding WX, Shen HM.
Title A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery.
Journal Nat Commun
Abstract PINK1-Parkin mediated mitophagy, a selective form of autophagy, represents one of the most important mechanisms in mitochondrial quality control (MQC) via the clearance of damaged mitochondria. Although it is well known that the conjugation of mammalian ATG8s (mATG8s) to phosphatidylethanolamine (PE) is a key step in autophagy, its role in mitophagy remains controversial. In this study, we clarify the role of the mATG8-conjugation system in mitophagy by generating knockouts of the mATG8-conjugation machinery. Unexpectedly, we show that mitochondria could still be cleared in the absence of the mATG8-conjugation system, in a process independent of lysosomal degradation. Instead, mitochondria are cleared via extracellular release through a secretory autophagy pathway, in a process we define as Autophagic Secretion of Mitochondria (ASM). Functionally, increased ASM promotes the activation of the innate immune cGAS-STING pathway in recipient cells. Overall, this study reveals ASM as a mechanism in MQC when the cellular mATG8-conjugation machinery is dysfunctional and highlights the critical role of mATG8 lipidation in suppressing inflammatory responses.
Volume 13(1)
Pages 3720
Published 2022-6-28
DOI 10.1038/s41467-022-31213-7
PII 10.1038/s41467-022-31213-7
PMID 35764633
PMC PMC9240011
MeSH Animals Autophagy Biological Transport Lysosomes / metabolism Mammals Mitochondria* / metabolism Mitophagy*
IF 12.121
Mice RBRC02759