CLPP and type 2 diabetes mellitus: As shown in Fig. 4I, TFA significantly reversed reduction of PGC-1α and p-AMPK/AMPK in diabetic mice (p < 0.01, vs T2DM); moreover, expression of mitochondria unfolded proteins including LONP1, CLPP, HSP60 and HSP70 were significantly increased by TFA to the level that was comparable to that of metformin (MET), suggesting TFA protected neuron function by promoting mitochondrial biogenesis and maintaining energy metabolic balance.