A Nuclear Pyruvate Dehydrogenase Complex Is Important for the Generation of Acetyl-CoA and Histone Acetylation
| Autor: | Trevor H. Stenson, Roxane Paulin, Adam Kinnaird, Gopinath Sutendra, Eric Flaim, Evangelos D. Michelakis, Nan Zhang, Kyoko Hashimoto, Peter Dromparis, Alois Haromy |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Lysine
Pyruvate Dehydrogenase Complex Mitochondrial pyruvate dehydrogenase complex macromolecular substances Mitochondrion General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Acetyl Coenzyme A Cell Line Tumor Humans Epigenetics 030304 developmental biology Cell Nucleus 0303 health sciences biology Biochemistry Genetics and Molecular Biology(all) Cell Cycle Acetyl-CoA hemic and immune systems Pyruvate dehydrogenase complex Mitochondria Protein Transport Histone Biochemistry chemistry Acetylation 030220 oncology & carcinogenesis biology.protein |
| Zdroj: | Cell. 158(1):84-97 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2014.04.046 |
| Popis: | SummaryDNA transcription, replication, and repair are regulated by histone acetylation, a process that requires the generation of acetyl-coenzyme A (CoA). Here, we show that all the subunits of the mitochondrial pyruvate dehydrogenase complex (PDC) are also present and functional in the nucleus of mammalian cells. We found that knockdown of nuclear PDC in isolated functional nuclei decreased the de novo synthesis of acetyl-CoA and acetylation of core histones. Nuclear PDC levels increased in a cell-cycle-dependent manner and in response to serum, epidermal growth factor, or mitochondrial stress; this was accompanied by a corresponding decrease in mitochondrial PDC levels, suggesting a translocation from the mitochondria to the nucleus. Inhibition of nuclear PDC decreased acetylation of specific lysine residues on histones important for G1-S phase progression and expression of S phase markers. Dynamic translocation of mitochondrial PDC to the nucleus provides a pathway for nuclear acetyl-CoA synthesis required for histone acetylation and epigenetic regulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|