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)/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.
Laboratory of Molecular Genetics, Department of Post-Genomics & Diseases, Osaka University Medical School, and Solution-Oriented Research for Science and Technology of Japan Science and Technology Corporation, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Rie
R
Sugioka
Shigeomi
S
Shimizu
Yoshihide
Y
Tsujimoto
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D034284:Dynamin I / Q000235:genetics / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014162:Transfection; D000098855:Collapsin Response Mediator Protein 1
D004247:DNA; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1