Energy Metabolism Under Stress: Late-Stage Leigh Syndrome Reveals Profound Cardiometabolic Perturbations in Ndufs4 KO Mice.

ABSTRACT: The deficiency of mitochondrial complex I (CI), a key regulator of cellular energy homeostasis and metabolic flexibility, is a prevalent driver of cardiovascular pathology in mitochondrial disorders. The Ndufs4 knockout (KO) mouse model of Leigh syndrome (LS), which lacks a critical CI subunit, exhibits severe cardiac abnormalities secondary to encephalomyopathy. However, the metabolic basis of LS-associated cardiac dysfunction remains poorly understood. This study aims to evaluate how whole-body CI deficiency affects cardiac bioenergetics and metabolism in late-stage Ndufs4 KO mice. We assessed respiratory chain enzyme activities and oxygen consumption rates using kinetic spectrophotometric assays and high-resolution respirometry, respectively, in mitochondria isolated from Ndufs4 KO and

SUBMITTER: Terburgh K 

PROVIDER: S-EPMC12801098 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature