Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis

Sugioka R, Shimizu S and Tsujimoto Y
Source: J Biol Chem
Publication Date: (2004)
Issue: 279(50): 52726-52734
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Species: human
Tissue Origin: cervix
Embryonic fibroblast, mouse (MEF) immort
Species: mouse
Tissue Origin: embryo
Nucleofector® I/II/2b
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.