Fumarate is a terminal electron acceptor in the mammalian electron transport chain.
Animals
Cell Hypoxia
Cell Line
Cell Line, Tumor
Dihydroorotate Dehydrogenase
/ metabolism
Electron Transport
Electron Transport Complex I
/ metabolism
Electron Transport Complex III
/ metabolism
Electron Transport Complex IV
/ metabolism
Electrons
Female
Fumarates
/ metabolism
Humans
Mice
Mice, Inbred C57BL
Mitochondria
/ metabolism
Oxidation-Reduction
Oxygen
/ metabolism
Succinate Dehydrogenase
/ metabolism
Ubiquinone
/ analogs & derivatives
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
03 Dec 2021
03 Dec 2021
Historique:
entrez:
2
12
2021
pubmed:
3
12
2021
medline:
18
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34855504
doi: 10.1126/science.abi7495
pmc: PMC8803114
mid: NIHMS1771049
doi:
Substances chimiques
Dihydroorotate Dehydrogenase
0
Fumarates
0
Ubiquinone
1339-63-5
Succinate Dehydrogenase
EC 1.3.99.1
Electron Transport Complex IV
EC 1.9.3.1
Electron Transport Complex I
EC 7.1.1.2
Electron Transport Complex III
EC 7.1.1.8
ubiquinol
M9NL0C577Y
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1237Subventions
Organisme : NIDDK NIH HHS
ID : F31 DK113665
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA234839
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA254162
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219859
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197532
Pays : United States
Commentaires et corrections
Type : CommentIn
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