Cytosolic and mitochondrial NADPH fluxes are independently regulated.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
11
02
2022
accepted:
02
02
2023
medline:
29
6
2023
pubmed:
28
3
2023
entrez:
27
3
2023
Statut:
ppublish
Résumé
Although nicotinamide adenine dinucleotide phosphate (NADPH) is produced and consumed in both the cytosol and mitochondria, the relationship between NADPH fluxes in each compartment has been difficult to assess due to technological limitations. Here we introduce an approach to resolve cytosolic and mitochondrial NADPH fluxes that relies on tracing deuterium from glucose to metabolites of proline biosynthesis localized to either the cytosol or mitochondria. We introduced NADPH challenges in either the cytosol or mitochondria of cells by using isocitrate dehydrogenase mutations, administering chemotherapeutics or with genetically encoded NADPH oxidase. We found that cytosolic challenges influenced NADPH fluxes in the cytosol but not NADPH fluxes in mitochondria, and vice versa. This work highlights the value of using proline labeling as a reporter system to study compartmentalized metabolism and reveals that NADPH homeostasis in the cytosolic and mitochondrial locations of a cell are independently regulated, with no evidence for NADPH shuttle activity.
Identifiants
pubmed: 36973440
doi: 10.1038/s41589-023-01283-9
pii: 10.1038/s41589-023-01283-9
doi:
Substances chimiques
NADP
53-59-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
837-845Subventions
Organisme : NIH HHS
ID : R24 OD024624
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES028365
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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