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

<p>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, <i>BCAT-1,</i> and the neurodegenerative movement disorder, Parkinson's disease (PD). RNAi-mediated knockdown of <i>C. elegans bcat-1</i> 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 <i>bcat-1 </i>knockdown increases mitochondrial respiration and induces oxidative damage in neurons through mTOR-independent mechanisms. Increased mitochondrial respiration, or 'mitochondrial hyperactivity,' is required for <i>bcat-1(RNAi)</i> neurotoxicity. Moreover, we show that post-disease onset administration of the type 2 diabetes medication, metformin, reduces mitochondrial respiration to control levels and significantly improves both motor function and neuronal viability. Together, our findings suggest that mitochondrial hyperactivity may be an early event in PD pathogenesis, and strategies aimed at reducing mitochondrial respiration may constitute a surprising new avenue for PD treatment.</p>