Nuclear Pyruvate Dehydrogenase Complex Generates Acetyl-CoA for Histone Acetylation

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

The mitochondrial pyruvate dehydrogenase complex (PDC) is a key enzyme in metabolism but also has a newly recognized functional role in the nucleus of mammalian cells.  Sutendra and colleagues have discovered that PDC translocates from the mitochondria to the nucleus  in a cell-cycle-dependent manner and in response to serum, epidermal growth factor, or mitochondrial stress.  Inhibition of nuclear PDC decreased acetylation of specific lysine residues on histones important for G1-S phase progression and expression of S phase markers.

In summary, DNA transcription, replication, and repair are regulated by histone acetylation, a process that requires the generation of acetyl-coenzyme A (CoA) that is provided by dynamic translocation of mitochondrial PDC to the nucleus.

Posted by Nicola Brunetti-Pierri, MD

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