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

Shun-Ichi Yamashita1, Xiulian Jin1, Kentaro Furukawa1

  • 1Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.

Insights

Mitochondrial division is not essential for mitophagy, but factors for autophagosome formation drive mitochondrial division during this process. This suggests a coordinated mechanism for mitophagy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Mitophagy is crucial for mitochondrial quality control.
  • It's traditionally thought that mitochondrial division precedes autophagosome formation.
  • The precise temporal relationship and interdependence of these events remain unclear.

Purpose of the Study:

  • To investigate the temporal relationship between mitochondrial division and autophagosome formation during mitophagy.
  • To determine the role of mitochondrial division factors (Dnm1/Drp1) in mitophagy.
  • To elucidate the involvement of autophagosome formation factors in mitochondrial division for mitophagy.

Main Methods:

  • Live-cell imaging in yeast and mammalian cells.
  • Genetic analysis using knockout/mutant strains for mitophagy and autophagosome factors.
  • Microscopy to observe mitochondrial dynamics and autophagosome formation.

Main Results:

  • The mitochondrial division factor Dnm1/Drp1 is dispensable for mitophagy.
  • Factors essential for autophagosome formation (FIP200, ATG14, WIPIs) are required for mitochondrial division during mitophagy.
  • Live-cell imaging revealed that isolation membranes form on mitochondria, and division occurs concurrently with membrane extension and autophagosome formation.

Conclusions:

  • Mitochondrial division is not a prerequisite for mitophagy.
  • Autophagosome formation machinery plays a direct role in mediating mitochondrial division for mitophagy.
  • Mitophagy involves a coordinated process where mitochondrial division and autophagosome formation occur simultaneously.

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