Oxygen Sensors at the Crossroad of Metabolism

被引:238
作者
Aragones, Julian [1 ,2 ]
Fraisl, Peter [1 ,2 ]
Baes, Myriam [3 ]
Carmeliet, Peter [1 ,2 ]
机构
[1] Katholieke Univ Leuven, Vesalius Res Ctr, B-3000 Louvain, Belgium
[2] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven, Lab Cell Metab, B-3000 Louvain, Belgium
关键词
HYDROXYLASE DOMAIN PROTEIN-2; INDUCIBLE FACTOR-I; MYOCARDIAL HIBERNATION; HYPOXIA TOLERANCE; CELL-METABOLISM; SENSING PATHWAY; PPAR-ALPHA; PROLYL; HIF; CANCER;
D O I
10.1016/j.cmet.2008.10.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aerobic organisms developed mechanisms to protect themselves against a shortage of oxygen (O-2). Recent studies reveal that O-2 sensors, belonging to the novel class of 2-oxoglutarate dependent iron(ii)-dioxygenases, have more important roles in metabolism than anticipated. Here, we provide a "metabolo-centric" overview of the role of the PHD/FIH members of this family in metabolism, in particular on how they regulate O-2 supply and consumption, energy compensation and conservation, O-2 conformance and hypoxia tolerance, redox and pH homeostasis, and other vital metabolic processes with implications in health and disease. These insights may offer novel opportunities for the treatment of ischemic diseases.
引用
收藏
页码:11 / 22
页数:12
相关论文
共 95 条
  • [31] Interstitial pH and pO(2) gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation
    Helmlinger, G
    Yuan, F
    Dellian, M
    Jain, RK
    [J]. NATURE MEDICINE, 1997, 3 (02) : 177 - 182
  • [32] Myocardial hibernation: a delicate balance
    Heusch, G
    Schulz, R
    Rahimtoola, SH
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 288 (03): : H984 - H999
  • [33] Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury
    Hill, Peter
    Shukla, Deepa
    Tran, Maxine G. B.
    Aragones, Julian
    Cook, H. Terence
    Carmeliet, Peter
    Maxwell, Patrick H.
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2008, 19 (01): : 39 - 46
  • [34] Hypoxia inhibits the peroxisome proliferator-activated receptor α/retinoid X receptor gene regulatory pathway in cardiac myocytes -: A mechanism for O2-dependent modulation of mitochondrial fatty acid oxidation
    Huss, JM
    Levy, FH
    Kelly, DP
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (29) : 27605 - 27612
  • [35] HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability
    Isaacs, JS
    Jung, YJ
    Mole, DR
    Lee, S
    Torres-Cabala, C
    Chung, YL
    Merino, M
    Trepel, J
    Zbar, B
    Toro, J
    Ratcliffe, PJ
    Linehan, WM
    Neckers, L
    [J]. CANCER CELL, 2005, 8 (02) : 143 - 153
  • [36] Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α
    Iyer, NV
    Kotch, LE
    Agani, F
    Leung, SW
    Laughner, E
    Wenger, RH
    Gassmann, M
    Gearhart, JD
    Lawler, AM
    Yu, AY
    Semenza, GL
    [J]. GENES & DEVELOPMENT, 1998, 12 (02) : 149 - 162
  • [37] Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway
    Kaelin, William G., Jr.
    Ratcliffe, Peter J.
    [J]. MOLECULAR CELL, 2008, 30 (04) : 393 - 402
  • [38] Prolyl hydroxylase inhibitor treatment confers whole-animal hypoxia tolerance
    Kasiganesan, H.
    Sridharan, V.
    Wright, G.
    [J]. ACTA PHYSIOLOGICA, 2007, 190 (02) : 163 - 169
  • [39] Induction of human endometrial cancer cell senescence through modulation of HIF-1α activity by EGLN1
    Kato, H
    Inoue, T
    Asanoma, K
    Nishimura, C
    Matsuda, T
    Wake, N
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (05) : 1144 - 1153
  • [40] HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia
    Kim, JW
    Tchernyshyov, I
    Semenza, GL
    Dang, CV
    [J]. CELL METABOLISM, 2006, 3 (03) : 177 - 185