Regulation of apoptosis by respiration: cytochrome c release by respiratory substrates.
Cytochrome c release from mitochondria is essential for apoptosis. Using human myelogenous leukemia ML-1a, its respiration-deficient and reconstituted cells, we demonstrated that respiratory function is essential for tumor necrosis factor-induced cytochrome c release. In a cell free system using mitochondrial fraction from ML-1a, initiation of respiration by substrates for complexes I, II, and III but not IV released cytochrome c, suggesting that reduction of coenzyme Q or complex III is essential for cytochrome c release. In the same system, disruption of mitochondrial outer membrane was neither enough nor the cause for cytochrome c release by succinate. These observations define an early pathway in which a change in respiration releases cytochrome c.
Nishimura
G
G
Department of Molecular Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Proske
R J
RJ
Doyama
H
H
Higuchi
M
M
D017209:Apoptosis / Q000502:physiology*; D002474:Cell-Free System; D003574:Cytochrome c Group / Q000378:metabolism*; D004579:Electron Transport; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D003574:Cytochrome c Group