PYCR1 and cancer: PYCR1 is a housekeeping enzyme that participates in the final step of proline biosynthesis by catalyzing P5C to proline.38 It locates in mitochondria, which mainly involved in the conversion of glutamate to proline in diseases, especially cancer.39 In addition, SIRT3 can increase enzymatic activity by directly binding and deacetylating PYCR1 at the K228 site,40 implying that the activation of SIRT3 may improve cardiac diseases by inhibiting PYCR1-mediated oxidative stress.