Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling.
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Publication Date
2018-09-04Journal Title
Cell Metab
ISSN
1550-4131
Publisher
Elsevier BV
Volume
28
Issue
3
Pages
525-531.e4
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Fedor, J. G., & Hirst, J. (2018). Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling.. Cell Metab, 28 (3), 525-531.e4. https://doi.org/10.1016/j.cmet.2018.05.024
Abstract
Mitochondrial respiratory supercomplexes, comprising complexes I, III, and IV, are the minimal functional units of the electron transport chain. Assembling the individual complexes into supercomplexes may stabilize them, provide greater spatiotemporal control of respiration, or, controversially, confer kinetic advantages through the sequestration of local quinone and cytochrome c pools (substrate channeling). Here, we have incorporated an alternative quinol oxidase (AOX) into mammalian heart mitochondrial membranes to introduce a competing pathway for quinol oxidation and test for channeling. AOX substantially increases the rate of NADH oxidation by O2 without affecting the membrane integrity, the supercomplexes, or NADH-linked oxidative phosphorylation. Therefore, the quinol generated in supercomplexes by complex I is reoxidized more rapidly outside the supercomplex by AOX than inside the supercomplex by complex III. Our results demonstrate that quinone and quinol diffuse freely in and out of supercomplexes: substrate channeling does not occur and is not required to support respiration.
Keywords
alternative oxidase, channeling, mitochondria, oxidative phosphorylation, respirasome, supercomplex, ubiquinone, Animals, Benzoquinones, Biocatalysis, Cattle, Cell Respiration, Electron Transport Complex I, Electron Transport Complex III, Electron Transport Complex IV, Female, Kinetics, Male, Mitochondria, Heart, Mitochondrial Membranes, Oxidation-Reduction, Oxidative Phosphorylation, Oxidoreductases
Sponsorship
Medical Research Council (MC_U105663141)
MRC (MC_UP_1002/1)
MRC (MC_UU_00015/2)
Identifiers
External DOI: https://doi.org/10.1016/j.cmet.2018.05.024
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282772
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