Metabolic costs and trade-offs of hypermetabolism in human motor neurons with ATP synthase deficiency.

ABSTRACT: Hypermetabolism, a futile cycle of energy production and consumption, has been proposed as an adaptative response to deficiencies in mitochondrial oxidative phosphorylation. However, the cellular costs of hypermetabolism remain largely unknown. Here we studied the consequences of hypermetabolism in human motor neurons harboring a heteroplasmic mutation in MT-ATP6, which impairs ATP synthase assembly. Respirometry, metabolomics, and proteomics analyses of the motor neurons showed that elevated ATP production rates were accompanied with increased demand for acetyl-Coenzyme A (acetyl-CoA) and depleted pantothenate (vitamin B5), and the proteome was remodeled to support the metabolic adaptation. Mitochondrial membrane potential and coupling efficiency remained stable, and the therapeutic agent

SUBMITTER: Torregrosa-Munumer R 

PROVIDER: S-EPMC12698834 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature