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Mfi2: an outer mitochondrial membrane mitofissin required for mitophagy

Kentaro Furukawa1, Tatsuro Maruyama2, Yuji Sakai3

  • 1Department of Cellular Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Autophagy Reports
|March 6, 2026
PubMed

Insights

Mitophagy requires mitochondrial fragmentation, but traditional fission factors are dispensable. New research reveals mitofissins, proteins on mitochondrial membranes, drive this essential fission process independently of Dnm1.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Mitophagy maintains cellular health by removing damaged mitochondria.
  • Mitochondrial fragmentation is crucial for mitophagy but its mechanism is unclear.
  • Known fission factors like Dnm1 are not essential for mitophagy.

Purpose of the Study:

  • To investigate the mechanism of mitochondrial fission during mitophagy.
  • To identify novel proteins involved in mitophagy-associated mitochondrial fragmentation.
  • To understand the role of mitofissins in mitophagy.

Main Methods:

  • Genetic analysis in yeast Saccharomyces cerevisiae.
  • Identification and characterization of mitochondrial outer membrane proteins.
  • Investigating protein function independently of Dnm1.

Main Results:

  • Mitofissins, a new class of proteins, are involved in mitochondrial fission during mitophagy.
  • Mitochondrial outer membrane protein Mfi2 (mitofissin 2) is essential for efficient mitophagy.
  • Mitofissin activity from both inner and outer mitochondrial membranes drives mitophagy-associated fission.

Conclusions:

  • Mitophagy-associated mitochondrial fission is mediated by mitofissins.
  • This process is independent of the canonical Dnm1 fission pathway.
  • Regulation of mitofissin activity and modulation by cardiolipin are key areas for future research.
Keywords:
Atg44Dnm1Mfi2mitochondrial fissionmitofissinmitophagy

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