Pregnancy precipitates metabolic imbalance and accelerates death in an animal model of mitochondrial cardiomyopathy

We observe cardiac remodeling, mitochondrial stress, and profound metabolic rewiring in PP mutant CHCHD10 hearts. Metabolic rewiring results decreased levels of heme and the depletion of key cofactors of energy metabolism, including NAD(H) and ADP. These findings suggest that mutant CHCHD10 hearts fail to meet the increased energy demands associated with the trial of labor due to the insufficient turnover rate of NAD+/NADH and ADP/ATP.

We propose that this metabolic insufficiency drives PP mortality in mutant CHCHD10 mice. In support of this hypothesis, dietary supplementation with nicotinamide riboside and pterostilbene, a naturally derived polyphenol, increased PP survival and cardiac energy metabolites in mutant CHCHD10 mice. Our work provides novel insights into the molecular mechanisms of PP cardiomyopathy associated with mitochondrial stress and suggests potential beneficiary effects of dietary NAD(H) supplementation.