Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling

Publication date: Available online 21 June 2018
Source:Cell Metabolism
Author(s): Justin G. Fedor, Judy Hirst
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.

Graphical abstract

Teaser

Mitochondrial respiratory supercomplexes catalyze aerobic respiration. One of the reasons proposed for their supramolecular organization is to facilitate rapid electron transfer between complexes I and III via quinone channeling. Fedor et al. demonstrate that this is not the case, and that quinone functions as a shared, freely exchanging pool in mitochondria.


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