Fumarate is a Terminal Electron Acceptor in the Mammalian Electron Transport Chain

Overview

Journal Science

Specialty Science

Date 2021 Dec 2

PMID 34855504

Citations 78

Authors

Jessica B Spinelli

Paul C Rosen

Hans-Georg Sprenger

Anna M Puszynska

Jessica L Mann

Julian M Roessler

Andrew L Cangelosi

Antonia Henne

Kendall J Condon

Tong Zhang

Tenzin Kunchok

Caroline A Lewis

Navdeep S Chandel

David M Sabatini

Affiliations

Soon will be listed here.

Abstract

For electrons to continuously enter and flow through the mitochondrial electron transport chain (ETC), they must ultimately land on a terminal electron acceptor (TEA), which is known to be oxygen in mammals. Paradoxically, we find that complex I and dihydroorotate dehydrogenase (DHODH) can still deposit electrons into the ETC when oxygen reduction is impeded. Cells lacking oxygen reduction accumulate ubiquinol, driving the succinate dehydrogenase (SDH) complex in reverse to enable electron deposition onto fumarate. Upon inhibition of oxygen reduction, fumarate reduction sustains DHODH and complex I activities. Mouse tissues display varying capacities to use fumarate as a TEA, most of which net reverse the SDH complex under hypoxia. Thus, we delineate a circuit of electron flow in the mammalian ETC that maintains mitochondrial functions under oxygen limitation.

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