biostudies-literatureMacColl Garfinkel ANSFNICHD NIH HHSNCATS NIH HHSNIA NIH HHSNIDDK NIH HHSNIDCD NIH HHSNHLBI NIH HHSNINDS NIH HHSNational Institutes of HealthNIGMS NIH HHSBiotechnology and Biological Sciences Research CouncilNational Science Foundation2597-2613.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC10840693biostudies-literatureUnknown58(22)An instructive role for metabolism in embryonic patterning is emerging, although a role for mitochondria is poorly defined. We demonstrate that mitochondrial oxidative metabolism establishes the embryonic patterning center, the Spemann-Mangold Organizer, via hypoxia-inducible factor 1α (Hif-1α) in Xenopus. Hypoxia or decoupling ATP production from oxygen consumption expands the Organizer by activating Hif-1α. In addition, oxygen consumption is 20% higher in the Organizer than in the ventral mesoderm, indicating an elevation in mitochondrial respiration. To reconcile increased mitochondrial respiration with activation of Hif-1α, we discovered that the "free" c-subunit ring of the F₁F_o ATP synthase creates an inner mitochondrial membrane leak, which decouples ATP producDevelopmental cellMitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus.PMC10840693T32DK007058R01GM148490K01AG054734UL1 TR001863R01NS112706R01 NS112706F31 HL140823RF1AG072484BB/W018284/1F31HL140823R01 NS099124R01 HL149746R01HD102186K01 AG054734R37 NS045876R01 GM148490R21 DC019948DGE-1762114R01 HD114493R01 AG072484T32GM007270R37NS045876RF1 AG072484T32 DK007058R01NS099124R01 NS045876T32 GM007270R01 HD102186Alavian KNWills AESmith PJSMacColl Garfinkel APatel JHShteyman AJonas EAMnatsakanyan NKhokha MKfalseMitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus.An instructive role for metabolism in embryonic patterning is emerging, although a role for mitochondria is poorly defined. We demonstrate that mitochondrial oxidative metabolism establishes the embryonic patterning center, the Spemann-Mangold Organizer, via hypoxia-inducible factor 1α (Hif-1α) in Xenopus. Hypoxia or decoupling ATP production from oxygen consumption expands the Organizer by activating Hif-1α. In addition, oxygen consumption is 20% higher in the Organizer than in the ventral mesoderm, indicating an elevation in mitochondrial respiration. To reconcile increased mitochondrial respiration with activation of Hif-1α, we discovered that the "free" c-subunit ring of the F₁F_o ATP synthase creates an inner mitochondrial membrane leak, which decouples ATP produc2023-01-01T00:00:00Z2023 Nov2026-06-01T20:28:14.019Z2025-04-05T19:59:05.004ZS-EPMC108406933767306310.1016/j.devcel.2023.08.015