Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy

Figure 2

Regulation of FOXO3a and TFEB transcriptional control of mitophagy by polyphenols. (a) Mitochondrial stress activates mitochondrial unfolded protein responses (UPR^MT) to upregulate expression of SIRT3. SIRT3 deacetylates transcription factor FOXO3a to promote its nuclear translocation. Resveratrol, betulin, and quercetin potentially influence FOXO3a activation via SIRT3 dependent or independent pathways. Mitochondrial stress also generates reactive oxygen species (ROS) to activate the lysosomal Ca²⁺ signalling and calcineurin to dephosphorylate TFEB and promote its nuclear translocation. Curcumin activates TFEB via mTORC1 inhibition. Urolithin A (UA) may modulate mitophagy transcriptome via regulating FOXO3a or TFEB activity. Once in the nucleus, FOXO3a and TFEB initiate transcription of autophagy-lysosomal and mitophagy genes to facilitate mitochondrial clearance. (b) Classification of polyphenols.

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