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
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.