Global ablation of the mitochondrial calcium uniporter increases glycolysis in cortical neurons subjected to energetic stressors.

ABSTRACT: The effects of global mitochondrial calcium (Ca²⁺) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca²⁺ handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca²⁺ uptake and Ca²⁺-induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage. Energetic stress enhanced glycolysis and depressed Complex I activity in global MCU null, relative to WT, cortical neurons. HI reduced forebrain NADH levels more in global MCU nulls than WT mice suggesting that increased glycolytic consumption of

SUBMITTER: Nichols M 

PROVIDER: S-EPMC5536808 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature