caa a22 4500 606175180 CHVBK 20210128100742.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00018-015-1978-z doi (NATIONALLICENCE)springer-10.1007/s00018-015-1978-z 2-Oxoglutarate-dependent dioxygenases are sensors of energy metabolism, oxygen availability, and iron homeostasis: potential role in the regulation of aging process [Elektronische Daten] [Antero Salminen, Anu Kauppinen, Kai Kaarniranta] Recent studies have revealed that the members of an ancient family of nonheme Fe2+/2-oxoglutarate-dependent dioxygenases (2-OGDO) are involved in the functions associated with the aging process. 2-Oxoglutarate and O2 are the obligatory substrates and Fe2+ a cofactor in the activation of 2-OGDO enzymes, which can induce the hydroxylation of distinct proteins and the demethylation of DNA and histones. For instance, ten-eleven translocation 1-3 (TET1-3) are the demethylases of DNA, whereas Jumonji C domain-containing histone lysine demethylases (KDM2-7) are the major epigenetic regulators of chromatin landscape, known to be altered with aging. The functions of hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD1-3) as well as those of collagen hydroxylases are associated with age-related degeneration. Moreover, the ribosomal hydroxylase OGFOD1 controls mRNA translation, which is known to decline with aging. 2-OGDO enzymes are the sensors of energy metabolism, since the Krebs cycle intermediate 2-oxoglutarate is an activator whereas succinate and fumarate are the potent inhibitors of 2-OGDO enzymes. In addition, O2 availability and iron redox homeostasis control the activities of 2-OGDO enzymes in tissues. We will briefly elucidate the catalytic mechanisms of 2-OGDO enzymes and then review the potential functions of the above-mentioned 2-OGDO enzymes in the control of the aging process. Springer Basel, 2015 Aging nationallicence Epigenetics nationallicence Longevity nationallicence Mitochondria nationallicence Oxidative stress nationallicence Senescence nationallicence Salminen Antero Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland aut Kauppinen Anu Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland aut Kaarniranta Kai Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland aut Cellular and Molecular Life Sciences Springer Basel 72/20(2015-10-01), 3897-3914 1420-682X 72:20<3897 2015 72 18 https://doi.org/10.1007/s00018-015-1978-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1978-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Salminen Antero Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Kauppinen Anu Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Kaarniranta Kai Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/20(2015-10-01), 3897-3914 1420-682X 72:20<3897 2015 72 18