biostudies-literatureUnknown11(10)van der Walt GDirect 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 resultinMetabolites658https://www.ebi.ac.uk/biostudies/studies/S-EPMC8537744biostudies-literatureSub-Cellular Metabolomics Contributes Mitochondria-Specific Metabolic Insights to a Mouse Model of Leigh Syndrome.PMC8537744Louw RLindeque JZvan der Walt GMason SfalseSub-Cellular Metabolomics Contributes Mitochondria-Specific Metabolic Insights to a Mouse Model of Leigh Syndrome.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 resultin2021-01-01T00:00:00Z2021 Sep2025-04-20T02:03:32.335Z2025-04-20T02:03:32.335ZS-EPMC85377443467737310.3390/metabo11100658