hFis1, a novel component of the mammalian mitochondrial fission machinery

Dominic I James1, Philippe A Parone, Yves Mattenberger

  • 1Department of Cell Biology, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.

Insights

We identified hFis1, a mammalian protein that drives mitochondrial fission. This process, regulated by Drp1, can lead to apoptosis, though Bcl-xL can block the cell death pathway.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Apoptosis

Background:

  • Mitochondrial morphology is regulated by a balance between fission and fusion processes.
  • Yeast Fis1p is a key protein involved in mitochondrial division.

Purpose of the Study:

  • To identify and characterize the mammalian orthologue of yeast Fis1p.
  • To investigate the role of this protein in mitochondrial fission and its connection to apoptosis.

Main Methods:

  • Overexpression of the identified mammalian protein (hFis1) in various cell types.
  • Utilizing a dominant-negative mutant of Drp1 (Drp1(K38A)) to inhibit fission.
  • Assessing cytochrome c release and apoptosis induction.
  • Evaluating the effect of Bcl-xL on these processes.

Main Results:

  • hFis1 localizes to the outer mitochondrial membrane and induces mitochondrial fission.
  • hFis1-induced fission is inhibited by Drp1(K38A).
  • Mitochondrial fragmentation by hFis1 leads to cytochrome c release and apoptosis.
  • Bcl-xL prevents cytochrome c release and apoptosis but not mitochondrial fragmentation.

Conclusions:

  • hFis1 is a component of the mammalian mitochondrial fission machinery.
  • Regulation of mitochondrial fission processes may play a role in initiating apoptosis.

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