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Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.

ABSTRACT: We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation of their fibroblasts showed elevated oxygen consumption and decreased mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in ATP5F1B, which encodes the β subunit of mitochondrial ATP synthase (also called complex V). In yeast, mutations affecting the same region loosen coupling between the proton motive force and ATP synthesis, resulting in high rates of mitochondrial respiration. Expression of the mutant allele in human cell lines recapitulates this phenotype. These data support an autosomal dominant mitochondrial uncoupling syndrome with hypermetabolism. (Funded by the National Institutes of Health.).

SUBMITTER: Ganetzky RD

PROVIDER: S-EPMC9754853 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation.

Ganetzky Rebecca D RD Markhard Andrew L AL Yee Irene I Clever Sheila S Cahill Alan A Shah Hardik H Grabarek Zenon Z To Tsz-Leung TL Mootha Vamsi K VK

The New England journal of medicine 20221001 15

We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation of their fibroblasts showed elevated oxygen consumption and decreased mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in <i>ATP5F1B</i>, which encodes the β subunit of mitochondrial ATP synthase (also called complex V). In yeast, mutations affecting the same region loosen coupling between the proton motive force and ATP synthesis, ...[more]

PMID: 36239646

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