Intra-mitochondrial poly(ADP-ribosyl)ation: Potential role for alpha-ketoglutarate dehydrogenase

Eszter Pankotai, Zsombor Lacza, Marianna Murányi, Csaba Szabó

    Research output: Contribution to journalArticle

    26 Scopus citations

    Abstract

    Poly(ADP-ribose) polymerase (PARP) is an intracellular enzyme involved in DNA repair and in building poly-ADP-ribose polymers on nuclear proteins using NAD+. While the majority of PARP resides in the nucleus, several studies indicated that PARP may also be located in the cytosol or in the mitochondrial matrix. In this study we found several poly-ADP-ribosylated proteins in isolated rat liver mitochondria following hydrogen peroxide (H2O2) or nitric oxide donor treatment. Protein poly-ADP-ribosylation was more intense in isolated mitochondria than in whole tissue homogenates and it was not associated with increased nuclear PARP activity. We identified five poly-ADP-ribose (PAR) positive mitochondrial bands by protein mass fingerprinting. All of the identified enzymes exhibited decreased activity or decreased levels following oxidative or nitrosative stress. One of the identified proteins is dihydrolipoamide dehydrogenase (DLDH), a component of the alpha-ketoglutarate dehydrogenase (KGDH) complex, which uses NAD+ as a substrate. This raised the possibility that KGDH may have a PARP-like enzymatic activity. The intrinsic PARP activity of KGDH and DLDH was confirmed using a colorimetric PARP assay kit and by the incubation of the recombinant enzymes with H2O2. The KGDH enzyme may, therefore, have a novel function as a PARP-like enzyme, which may play a role in regulating intramitochondrial NAD+ and poly(ADP-ribose) homeostasis, with possible roles in physiology and pathophysiology.

    Original languageEnglish (US)
    Pages (from-to)159-164
    Number of pages6
    JournalMitochondrion
    Volume9
    Issue number2
    DOIs
    StatePublished - Apr 1 2009

    Keywords

    • Alpha-ketoglutarate dehydrogenase
    • Dihydrolipoamide dehydrogenase
    • Mitochondria
    • Nitric oxide
    • Oxidative stress
    • Poly(ADP-ribose) polymerase

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Cell Biology

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