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

Hayden Weng Siong Tan1, Guang Lu2, Han-Ming Shen1,3

  • 1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Autophagy
|July 28, 2022
PubMed

Insights

The mammalian Atg8 conjugation system is not required for PINK1-PRKN-mediated mitophagy. Instead, mitochondria are cleared via autophagic secretion of mitochondria (ASM), which may promote inflammation if defective.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • Mitophagy is crucial for mitochondrial quality control, clearing damaged mitochondria via the PINK1-PRKN pathway.
  • The conjugation of mammalian Atg8-family proteins (mATG8s) to phosphatidylethanolamine (PE) is a hallmark of autophagy, but its role in mitophagy is not well understood.

Purpose of the Study:

  • To investigate the role of the mATG8 conjugation system in PINK1-PRKN-mediated mitophagy.
  • To identify alternative mechanisms of mitochondria clearance.

Main Methods:

  • Utilized genetic and biochemical approaches to assess mitochondria clearance.
  • Investigated the involvement of secretory autophagy and the CGAS-STING1 pathway.

Main Results:

  • The mATG8 conjugation system is dispensable for PINK1-PRKN-mediated mitochondria clearance.
  • Mitochondria are cleared independently of mATG8 conjugation through a process termed autophagic secretion of mitochondria (ASM).
  • ASM leads to aberrant activation of the CGAS-STING1 pathway.

Conclusions:

  • PINK1-PRKN-mediated mitophagy does not require mATG8 conjugation.
  • Autophagic secretion of mitochondria (ASM) represents an alternative mitochondria clearance pathway.
  • Defects in mATG8 lipidation may trigger inflammation via ASM-induced CGAS-STING1 pathway activation.
Keywords:
Extracellular vesiclesPINK1-PRKNinflammationmATG8 conjugation systemmitochondrial quality controlmitophagysecretory autophagy

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