Fzo1, a Protein Involved in Mitochondrial Fusion, Inhibits Apoptosis

Mitochondrial morphology and physiology are regulated by the processes of fusion and fission. Some forms of apoptosis are reported to be associated with mitochondrial fragmentation. We showed that overexpression of Fzo1A/B (rat) proteins involved in mitochondrial fusion, or silencing of Dnm1 (rat)/D...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-12, Vol.279 (50), p.52726-52734
Main Authors: Sugioka, Rie, Shimizu, Shigeomi, Tsujimoto, Yoshihide
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Base Sequence
Cells, Cultured
DNA - genetics
Dynamin I - genetics
Dynamin I - physiology
Gene Silencing
GTP Phosphohydrolases - genetics
GTP Phosphohydrolases - physiology
HeLa Cells
Humans
Membrane Fusion
Mice
Mitochondria - physiology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - physiology
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
RNA, Small Interfering - genetics
Transfection
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Summary:Mitochondrial morphology and physiology are regulated by the processes of fusion and fission. Some forms of apoptosis are reported to be associated with mitochondrial fragmentation. We showed that overexpression of Fzo1A/B (rat) proteins involved in mitochondrial fusion, or silencing of Dnm1 (rat)/Drp1 (human) (a mitochondrial fission protein), increased elongated mitochondria in healthy cells. After apoptotic stimulation, these interventions inhibited mitochondrial fragmentation and cell death, suggesting that a process involved in mitochondrial fusion/fission might play a role in the regulation of apoptosis. Consistently, silencing of Fzo1A/B or Mfn1/2 (a human homolog of Fzo1A/B) led to an increase of shorter mitochondria and enhanced apoptotic death. Overexpression of Fzo1 inhibited cytochrome c release and activation of Bax/Bak, as assessed from conformational changes and oligomerization. Silencing of Mfn or Drp1 caused an increase or decrease of mitochondrial sensitivity to apoptotic stimulation, respectively. These results indicate that some of the proteins involved in mitochondrial fusion/fission modulate apoptotic cell death at the mitochondrial level.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M408910200