Abstract:
:In this study we report the identification of FAH domain containing protein 1 (FAHD1), a recently described member of the fumarylacetoacetate hydrolase (FAH) superfamily of metabolic enzymes, as a novel player in the regulation of cellular senescence. FAHD1 was found in a proteomic screen searching for mitochondrial proteins, which are differentially regulated in mitochondria from young and senescent human endothelial cells, and subsequently identified as oxaloacetate decarboxylase. We report here that depletion of FAHD1 from human endothelial cells inhibited mitochondrial energy metabolism and subsequently induced premature senescence. Whereas senescence induced by FAHD1 depletion was not associated with DNA damage, we noted a reduction of mitochondrial ATP-coupled respiration associated with upregulation of the cdk inhibitor p21. These results indicate that FAHD1 is required for mitochondrial function in human cells and provide additional support to the growing evidence that mitochondrial dysfunction can induce cellular senescence by metabolic alterations independent of the DNA damage response pathway.
journal_name
Exp Gerontoljournal_title
Experimental gerontologyauthors
Petit M,Koziel R,Etemad S,Pircher H,Jansen-Dürr Pdoi
10.1016/j.exger.2017.03.004subject
Has Abstractpub_date
2017-06-01 00:00:00pages
7-12eissn
0531-5565issn
1873-6815pii
S0531-5565(16)30457-0journal_volume
92pub_type
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