IDH2 and cancer: Although NADH, rather than NAD+, accumulates in the mitochondrial matrix of highly glycolytic cancer cells in which OXPHOS is dormant (Figure 2(a)), NAD+ might be produced by the inner membrane H+ transhydrogenase from NADH with the simultaneous formation of NADPH from NADP+ in the matrix [67], thereby activating SIRT3-mediated IDH2 deacetylation.