NRF1 and proximal spinal muscular atrophy: We also investigated markers associated with mitochondrial biogenesis and function in muscle (Pgc1-α, Tfam, Ndufs1, and Nrf1), as previous research has established that these features are impaired in SMA skeletal muscle [46] and a common mechanism of action for metformin is mild inhibition of mitochondrial electron transport complex 1 (or NADH:ubiquinone oxidoreductase) [77].