Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function.

The positive role of in regulation of various nuclear DNA transactions is well established. Although a mitochondrial localization of Pduanyu371 has been suggested, its role in the maintenance of the mitochondrial DNA is currently unknown. Here we investigated the role of Pduanyu371 in the repair of the mitochondrial DNA in the baseline and oxidative stress conditions. We used wild-type A549 cells or cells depleted of Our data show that intra-mitochondrial Pduanyu371 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Polγ), which under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction between mitochondrial BER enzymes was significantly affected in the presence of Pduanyu371. Moreover, the repair of the oxidative-induced damage to the mitochondrial DNA in cells was found to be more robust compared to control counterpart. In addition, mitochondrial biogenesis was enhanced in Pduanyu371-depleted cells, including mitochondrial DNA copy number and mitochondrial membrane potential. This observation was further confirmed by analysis of lung tissue isolated from WT and Pduanyu371 KO mice. In summary, we conclude that mitochondrial in opposite to nuclear Pduanyu371, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA.

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