Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy

J Cell Biol. 2016 Dec 5;215(5):649-665. doi: 10.1083/jcb.201605093. Epub 2016 Nov 30.

Abstract

Mitophagy is thought to play an important role in mitochondrial quality control. Mitochondrial division is believed to occur first, and autophagosome formation subsequently occurs to enwrap mitochondria as a process of mitophagy. However, there has not been any temporal analysis of mitochondrial division and autophagosome formation in mitophagy. Therefore, the relationships among these processes remain unclear. We show that the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy. Autophagosome formation factors, such as FIP200, ATG14, and WIPIs, were essential for the mitochondrial division for mitophagy. Live-cell imaging showed that isolation membranes formed on the mitochondria. A small portion of the mitochondria then divided from parental mitochondria simultaneously with the extension of isolation membranes and autophagosome formation. These findings suggest the presence of a mitophagy process in which mitochondrial division for mitophagy is accomplished together with autophagosome formation.

MeSH terms

  • Animals
  • Autophagosomes / drug effects
  • Autophagosomes / metabolism*
  • Autophagosomes / ultrastructure
  • Deferiprone
  • Dynamins
  • GTP Phosphohydrolases / metabolism*
  • HeLa Cells
  • Humans
  • Mammals / metabolism
  • Microtubule-Associated Proteins / metabolism*
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / metabolism*
  • Mitophagy* / drug effects
  • Models, Biological
  • Pyridones / pharmacology
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / metabolism
  • Time-Lapse Imaging

Substances

  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Pyridones
  • Saccharomyces cerevisiae Proteins
  • Deferiprone
  • GTP Phosphohydrolases
  • DNM1 protein, S cerevisiae
  • DNM1L protein, human
  • Dynamins