Enhanced glycolysis and GSK3 inactivation promote brain metabolic adaptations following neuronal mitochondrial stress.

ABSTRACT: We analyzed early brain metabolic adaptations in response to mitochondrial dysfunction in a mouse model of mitochondrial encephalopathy with complex IV deficiency [neuron-specific COX10 knockout (KO)]. In this mouse model, the onset of the mitochondrial defect did not coincide with immediate cell death, suggesting early adaptive metabolic responses to compensate for the energetic deficit. Metabolomic analysis in the KO mice revealed increased levels of glycolytic and pentose phosphate pathway intermediates, amino acids and lysolipids. Glycolysis was modulated by enhanced activity of glycolytic enzymes, and not by their overexpression, suggesting the importance of post-translational modifications in the adaptive response. Glycogen synthase kinase 3 inactivation was the most upstream regulat

SUBMITTER: Garcia S 

PROVIDER: S-EPMC9077416 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature