Mitochondrial PARP1 Regulates Mitochondrial DNA and Aging: Preclinical Findings

Synopsis

Scientists have discovered that the enzyme PARP1, known for repairing DNA in the cell nucleus, is also active inside mitochondria, where it helps control mitochondrial DNA (mtDNA). Using purified mitochondria, researchers showed that adding NAD+, the molecule PARP1 depends on, triggered a process called PARylation that regulates mtDNA transcription. Blocking this activity with the PARP inhibitor olaparib stopped PARylation, confirming PARP1’s role in mitochondrial function. The study found that mitochondrial PARP1 (mtPARP1) binds to mtDNA and influences the activity of TFAM, a key protein in mitochondrial gene expression. These results show that PARP1 uses NAD+ to coordinate mitochondrial DNA maintenance and energy production, offering new insights into how DNA repair, metabolism, and aging are connected.

Journal

Experimental & Molecular Medicine