Data associated with 'Metformin rescues Parkinson’s disease phenotypes caused by hyperactive mitochondria'

Metabolic dysfunction occurs in many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood. We recently discovered a potential causal link between the branched-chain amino acid transferase, BCAT-1, and the neurodegenerative movement disorder, Parkinson’s disease (PD). RNAi-mediated knockdown of C. elegans bcat-1 recapitulates PD-like features, including progressive motor deficits and neurodegeneration with age, yet the underlying mechanisms have remained unknown. Using transcriptomic, metabolomic, and imaging approaches, we show here that bcat-1 knockdown increases mitochondrial respiration and induces oxidative damage in neurons through mTOR-independent mechanisms. Increased mitochondrial respiration, or ‘mitochondrial hyperactivity,’ is required for bcat-1(RNAi) neurotoxicity. Moreover, we show that post-disease onset administration of the type 2 diabetes medication, metformin, reduces mitochondrial respiration to control levels and signifi...