2-Oxoglutarate-dependent dioxygenases are sensors of energy metabolism, oxygen availability, and iron homeostasis: potential role in the regulation of aging process

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• 作者：Antero Salminen ; Anu Kauppinen ; Kai Kaarniranta
• 关键词：Aging ; Epigenetics ; Longevity ; Mitochondria ; Oxidative stress ; Senescence
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：72
• 期：20
• 页码：3897-3914
• 全文大小：694 KB
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• 作者单位：Antero Salminen (1)
  Anu Kauppinen (2) (3)
  Kai Kaarniranta (2) (3)
  
  1. Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland
  2. Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland
  3. Department of Ophthalmology, Kuopio University Hospital, P.O.B. 100, 70029, Kuopio, Finland
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

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. Keywords Aging Epigenetics Longevity Mitochondria Oxidative stress Senescence