Control of mitochondrial respiration: A quantitative evaluation of the roles of cytochrome c and oxygen

David F. Wilson, Charles S. Owen, Andrij Holian

Research output: Contribution to journalArticlepeer-review

Abstract

The dependence of the mitochondrial respiratory rate on the reduction of cytochrome c has been measured as a function of the exogenous [ATP] [ADP][Pi] ratio and pH. The respiratory rate at [ADP] [ADP][Pi] values of less than 10-1 m-1 is proportional to the reduction of cytochrome c and independent of pH from pH 6.5 to pH 8.O. The maximal turnover number (at 100% reduction) for cytochrome c is approximately 70 s-1. As the [ATP] [ADP][Pi] ratio is increased from 10-1 m-1 to 104 m-1, the respiration at any given level of reduction of cytochrome c is progressively inhibited. Greater inhibition is observed at more oxidized levels of cytochorme c with respiratory control values for oxidation of reduced cytochrome c exceeding 10. The behavior of mitochondrial respiratory control is shown to be quantitatively consistent with a proposed mechanism in which the regulation occurs in the reaction of oxygen with cytochrome oxidase. A steady-state rate expression is derived which fits the mitochondrial respiratory rate dependence on (i) the extramitochondrial [ATP] [ADP][Pi] ratio; (ii) the level of reduction of cytochrome c (or the intramitochondrial [NAD+] [NADH]) at different [ATP] [ADP][Pi] values; (iii) the pH of the suspending medium. This rate expression appears to correctly predict the relationships of the cytoplasmic [ATP] [ADP][Pi] ratio, the mitochondrial [NAD+] [NADH] ratio, and the mitochondrial respiratory rate in intact cells as well as suspensions of isolated mitochondria.

Original languageEnglish
Pages (from-to)749-762
Number of pages14
JournalArchives of Biochemistry and Biophysics
Volume182
Issue number2
DOIs
StatePublished - Aug 1977

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