Figure 2.

Age‐related alteration in cyclophilin D (CypD) regulation promotes mPTP opening. In mitochondria from young animals, CypD, the main regulator of mPTP, is inhibited by the Hsp90‐related mitochondrial matrix protein Trap1 and sirtuin 3 (SIRT3). CypD is no longer inhibited by association with Trap1 and deacetylation by sirtuin 3. The drop in NAD ⁺ pool inhibits SIRT3 deacetylase activity, and translocation of p53 activates CypD by displacing it from Trap1, favoring the translocation of the protein to the mPTP complex. ANT, adenine nucleotide translocase; TSPO, translocator protein; Ac, acetyl; ┴, inhibition; (+)→, stimulation