title: Regulation of apoptosis by respiration: cytochrome c release by respiratory substrates.
abstract: 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.
authors.affiliation: Department of Molecular Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: G
authors.initials: G
authors.lastname: Nishimura
authors.forename: R J
authors.initials: RJ
authors.lastname: Proske
authors.forename: H
authors.initials: H
authors.lastname: Doyama
authors.forename: M
authors.initials: M
authors.lastname: Higuchi
mesh_terms: 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
chemical_list: D003574:Cytochrome c Group