Fig. 3.

Resveratrol activates AMP-activated protein kinase (AMPK), leading to an increase in cellular NAD + levels, which subsequently activates SIRT1 [116]. This dual activation of AMPK and SIRT1 together promotes mitochondrial biogenesis through the activation of PGC-1α [118]. Bezafibrate, on the other hand, activates peroxisome proliferator-activated receptors (PPARs) and enhances respiratory capacity while protecting against oxidative damage [112]. Pioglitazone, a PPARγ agonist, stimulates PPAR and TFAM expression [122], mitigating the inflammatory response by partially inhibiting NF-κB activation [123]. Additionally, bortezomib prevents the degradation of unbound (DNA-free) TFAM [98], which is central to mitochondrial biogenesis, suggesting therapeutic potential in preserving TFAM integrity.