Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria
| Autor: | Dierk Jorcke, Siham M.A. Bakhit, Mathias Ziegler, Christoph Weise, Manfred Schweiger, Andrés Herrero-Yraola, Peter Franke |
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| Rok vydání: | 2001 |
| Předmět: |
Cations
Divalent Protein subunit Molecular Sequence Data Mitochondria Liver Biology Mitochondrion Guanosine Diphosphate Article General Biochemistry Genetics and Molecular Biology Glutamate Dehydrogenase Hydrolase Animals Magnesium Amino Acid Sequence Molecular Biology chemistry.chemical_classification Adenosine Diphosphate Ribose General Immunology and Microbiology General Neuroscience Glutamate dehydrogenase NAD Molecular biology Adenosine Diphosphate Enzyme chemistry Biochemistry ADP-ribosylation Cattle NAD+ kinase NADP Cysteine |
| Zdroj: | The EMBO Journal. 20:2404-2412 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/20.10.2404 |
| Popis: | Mitochondrial ADP-ribosylation leads to modification of two proteins of approximately 26 and 53 kDA: The nature of these proteins and, hence, the physiological consequences of their modification have remained unknown. Here, a 55 kDa protein, glutamate dehydrogenase (GDH), was established as a specific acceptor for enzymatic, cysteine-specific ADP-ribosylation in mitochondria. The modified protein was isolated from the mitochondrial preparation and identified as GDH by N-terminal sequencing and mass spectrometric analyses of tryptic digests. Incubation of human hepatoma cells with [14C]adenine demonstrated the occurrence of the modification in vivo. Purified GDH was ADP-ribosylated in a cysteine residue in the presence of the mitochondrial activity that transferred the ADP-ribose from NAD+ onto the acceptor site. ADP- ribosylation of GDH led to substantial inhibition of its catalytic activity. The stoichiometry between incorporated ADP-ribose and GDH subunits suggests that modification of one subunit per catalytically active homohexamer causes the inactivation of the enzyme. Isolated, ADP-ribosylated GDH was reactivated by an Mg2+-dependent mitochondrial ADP-ribosylcysteine hydrolase. GDH, a highly regulated enzyme, is the first mitochondrial protein identified whose activity may be modulated by ADP-ribosylation. |
| Databáze: | OpenAIRE |
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