Article: Unstable NAD+ Metabolism Leads to Impaired Heart Mitochondrial Function: Preclinical Findings

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Cardiovascular Disease Cardiovascular Health Mitochondrial Health Preclinical

Unstable NAD+ Metabolism Leads to Impaired Heart Mitochondrial Function: Preclinical Findings

Synopsis

Poly(ADP-ribose) polymerase (PARP) enzymes repair DNA but use NAD+ as fuel. Excessive DNA damage in heart cell mitochondria can overactivate PARP, depleting NAD+ and impairing mitochondrial function. In a mouse model with high mitochondrial DNA damage, NAD+ loss reduced activity of the mitochondrial regulator SIRT3. High doses of NR in this context worsened problems by causing nicotinamide buildup, further blocking sirtuins and altering mitochondrial structure. This suggests that while NR can be beneficial, high doses should be used cautiously when mitochondrial DNA instability is present.

Journal

eLife

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