Figure 3.

Hypothetical mechanisms of urolithin A in inducing mitophagy. Urolithin A activates SIRT1, SIRT3 [216] and AMPK. Activated AMPK increases PGC-1α levels [108] that directly increases mitochondrial biogenesis, which is in equilibrium with the mitophagy process. Activated AMPK also increases the activation of ULK1 [66]. Inhibition of mTOR1 is triggered by both urolithin A [217] and AMPK, which then activates ULK1 towards inducing mitophagy. The mTOR1 inhibition by Urolithin A may also induce the transcriptional activation of mitophagy via TFEBs. Urolithin A transcriptionally activates mitophagy via SIRT3-dependent FOXO activation [218,219].