Abstract：
:DNA 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.
journal_name
Celljournal_title
Cellauthors
Sutendra G,Kinnaird A,Dromparis P,Paulin R,Stenson TH,Haromy A,Hashimoto K,Zhang N,Flaim E,Michelakis EDdoi
10.1016/j.cell.2014.04.046subject
Has Abstractpub_date
2014-07-03 00:00:00pages
84-97issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(14)00674-6journal_volume
158pub_type
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