Mitochondrial respiratory chain inhibitors induce apoptosis.
In this paper the specific mitochondrial respiratory chain inhibitors rotenone and antimycin A and the highly specific mitochondrial ATP-synthase inhibitor oligomycin are shown to induce an apoptotic suicide response in cultured human lymphoblastoid and other mammalian cells within 12-18 h. The mitochondrial inhibitors do not induce apoptosis in cells depleted of mitochondrial DNA and thus lacking an intact mitochondrial respiratory chain. Apoptosis induced by respiratory chain inhibitors is not inhibited by the presence of Bcl-2. We discuss the possible role of mitochondrial induced apoptosis in the ageing process and age-associated diseases.
Wolvetang
E J
EJ
Department of Biochemistry, Monash University, Clayton, Vic., Australia.
Johnson
K L
KL
Krauer
K
K
Ralph
S J
SJ
Linnane
A W
AW
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D003470:Culture Media; D004247:DNA / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007938:Leukemia; D008545:Melanoma; D051379:Mice; D009840:Oligomycins / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012402:Rotenone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D009840:Oligomycins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012402:Rotenone; D000968:Antimycin A; D004247:DNA