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Published on: May 4, 2013
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.
Abstract:
The balance between the fission and fusion mechanisms regulate the morphology of mitochondria. In this study we have identified a mammalian protein that we call hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division. hFis1, when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission. This event was inhibited by a dominant negative mutant of Drp1 (Drp1(K38A)), a major component of the fission apparatus. Fragmentation of the mitochondrial network by hFis1 was followed by the release of cytochrome c and ultimately apoptosis. Bcl-xL was able to block cytochrome c release and apoptosis but failed to prevent mitochondrial fragmentation. Our studies show that hFis1 is part of the mammalian fission machinery and suggest that regulation of the fission processes might be involved in apoptotic mechanisms.
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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