Figure 5. Regulation of the mPTP by SIRT3. In normal cardiac tissue, SIRT3 targets CypD, maintaining it in a deacetylated state, thus preventing opening of the mPTP during aging and induced cardiac stress. In SIRT3−/− mice, however, CypD is hyperacetylated, resulting in increased induction of the mPTP. A decline in SIRT3 activity over time explains the increase in mitochondrial permeability transition and the decline in cardiac function with age. IMS = inner membrane space.