| Literature DB >> 34855504 |
Jessica B Spinelli1,2, Paul C Rosen1,2,3, Hans-Georg Sprenger1,2, Anna M Puszynska1,2, Jessica L Mann1,2,3, Julian M Roessler1,2,3, Andrew L Cangelosi1,2,3, Antonia Henne1, Kendall J Condon1,2,3, Tong Zhang1,2,3, Tenzin Kunchok1, Caroline A Lewis1, Navdeep S Chandel4, David M Sabatini3.
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.Entities:
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Year: 2021 PMID： 34855504 PMCID： PMC8803114 DOI： 10.1126/science.abi7495
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714