title: 2-Oxoglutarate-dependent dioxygenases are sensors of energy metabolism, oxygen availability, and iron homeostasis: potential role in the regulation of aging process.
abstract: Recent studies have revealed that the members of an ancient family of nonheme Fe(2+)/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 Fe(2+) 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.
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. antero.salminen@uef.fi.
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.|Department of Ophthalmology, Kuopio University Hospital, P.O.B. 100, 70029, Kuopio, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. kai.kaarniranta@uef.fi.|Department of Ophthalmology, Kuopio University Hospital, P.O.B. 100, 70029, Kuopio, Finland. kai.kaarniranta@uef.fi.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D019175:DNA Methylation; D049308:Dioxygenases / Q000378:metabolism / Q000502:physiology*; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D006706:Homeostasis; D000860:Hypoxia / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D014176:Protein Biosynthesis
chemical_list: D007501:Iron; D049308:Dioxygenases; D010100:Oxygen
keywords: Aging; Epigenetics; Longevity; Mitochondria; Oxidative stress; Senescence