Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling.


Type
Article
Change log
Authors
Fedor, Justin G 
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.

Description
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
Journal Title
Cell Metab
Conference Name
Journal ISSN
1550-4131
1932-7420
Volume Title
28
Publisher
Elsevier BV
Sponsorship
Medical Research Council (MC_U105663141)
MRC (MC_UP_1002/1)
MRC (MC_UU_00015/2)