Sub-Cellular Metabolomics Contributes Mitochondria-Specific Metabolic Insights to a Mouse Model of Leigh Syndrome.

ABSTRACT: Direct injury of mitochondrial respiratory chain (RC) complex I by Ndufs4 subunit mutations results in complex I deficiency (CID) and a progressive encephalomyopathy, known as Leigh syndrome. While mitochondrial, cytosolic and multi-organelle pathways are known to be involved in the neuromuscular LS pathogenesis, compartment-specific metabolomics has, to date, not been applied to murine models of CID. We thus hypothesized that sub-cellular metabolomics would be able to contribute organelle-specific insights to known Ndufs4 metabolic perturbations. To that end, whole brains and skeletal muscle from late-stage Ndufs4 mice and age/sex-matched controls were harvested for mitochondrial and cytosolic isolation. Untargeted 1H-NMR and semi-targeted LC-MS/MS metabolomics was applied to the resultin

SUBMITTER: van der Walt G 

PROVIDER: S-EPMC8537744 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature