Pharmacological approaches to restore mitochondrial function

被引:309
作者
Andreux, Penelope A. [1 ]
Houtkooper, Riekelt H. [2 ]
Auwerx, Johan [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland
[2] Univ Amsterdam, Acad Med Ctr, Lab Genet & Metab Dis, NL-1105 AZ Amsterdam, Netherlands
基金
瑞士国家科学基金会; 美国国家卫生研究院;
关键词
CYTOCHROME-C-OXIDASE; TRANSCRIPTIONAL COREPRESSOR RIP140; SMALL-MOLECULE ACTIVATORS; GENOME-WIDE ASSOCIATION; HUMAN SKELETAL-MUSCLE; FATTY-ACID OXIDATION; LIFE-SPAN EXTENSION; PPAR-GAMMA LIGAND; RECEPTOR-ALPHA; ERR-ALPHA;
D O I
10.1038/nrd4023
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders but also implicated in age-related diseases, including those that affect the metabolic and nervous system, such as type 2 diabetes and Parkinson's disease. Numerous pathways maintain and/or restore proper mitochondrial function, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response. New and powerful phenotypic assays in cell-based models as well as multicellular organisms have been developed to explore these different aspects of mitochondrial function. Modulating mitochondrial function has therefore emerged as an attractive therapeutic strategy for several diseases, which has spurred active drug discovery efforts in this area.
引用
收藏
页码:465 / 483
页数:19
相关论文
共 249 条
  • [1] ERRγ directs and maintains the transition to oxidative metabolism in the postnatal heart
    Alaynick, William A.
    Kondo, Richard P.
    Xie, Wen
    He, Weimin
    Dufour, Catherine R.
    Downes, Michael
    Jonker, Johan W.
    Giles, Wayne
    Naviaux, Robert K.
    Giguere, Vincent
    Evans, Ronald M.
    [J]. CELL METABOLISM, 2007, 6 (01) : 13 - 24
  • [2] Gradual alteration of mitochondrial structure and function by β-amyloids:: Importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release
    Aleardi, AM
    Benard, G
    Augereau, O
    Malgat, M
    Talbot, JC
    Mazat, JP
    Letellier, T
    Dachary-Prigent, J
    Solaini, GC
    Rossignol, R
    [J]. JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 2005, 37 (04) : 207 - 225
  • [3] OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28
    Alexander, C
    Votruba, M
    Pesch, UEA
    Thiselton, DL
    Mayer, S
    Moore, A
    Rodriguez, M
    Kellner, U
    Leo-Kottler, B
    Auburger, G
    Bhattacharya, SS
    Wissinger, B
    [J]. NATURE GENETICS, 2000, 26 (02) : 211 - 215
  • [4] Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits
    Andreux, Penelope A.
    Williams, Evan G.
    Koutnikova, Hana
    Houtkooper, Riekelt H.
    Champy, Marie-France
    Henry, Hugues
    Schoonjans, Kristina
    Williams, Robert W.
    Auwerx, Johan
    [J]. CELL, 2012, 150 (06) : 1287 - 1299
  • [5] Upregulated function of mitochondria-associated ER membranes in Alzheimer disease
    Area-Gomez, Estela
    Castillo, Maria Del Carmen Lara
    Tambini, Marc D.
    Guardia-Laguarta, Cristina
    de Groof, Ad J. C.
    Madra, Moneek
    Ikenouchi, Junichi
    Umeda, Masato
    Bird, Thomas D.
    Sturley, Stephen L.
    Schon, Eric A.
    [J]. EMBO JOURNAL, 2012, 31 (21) : 4106 - 4123
  • [6] Improving metabolism by increasing energy expenditure
    Auwerx, J
    [J]. NATURE MEDICINE, 2006, 12 (01) : 44 - 45
  • [7] PARP-1 Inhibition Increases Mitochondrial Metabolism through SIRT1 Activation
    Bai, Peter
    Canto, Caries
    Oudart, Hugues
    Brunyanszki, Attila
    Cen, Yana
    Thomas, Charles
    Yamamoto, Hiroyasu
    Huber, Aline
    Kiss, Borbala
    Houtkooper, Riekelt H.
    Schoonjans, Kristina
    Schreiber, Valerie
    Sauve, Anthony A.
    Menissier-de Murcia, Josiane
    Auwerx, Johan
    [J]. CELL METABOLISM, 2011, 13 (04) : 461 - 468
  • [8] The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity
    Barbosa, Maria Thereza P.
    Soares, Sandra M.
    Novak, Colleen M.
    Sinclair, David
    Levine, James A.
    Aksoy, Pinar
    Chini, Eduardo Nunes
    [J]. FASEB JOURNAL, 2007, 21 (13) : 3629 - 3639
  • [9] Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons
    Barsoum, Mark J.
    Yuan, Hua
    Gerencser, Akos A.
    Liot, Geraldine
    Kushnareva, Yulia E.
    Graeber, Simone
    Kovacs, Imre
    Lee, Wilson D.
    Waggoner, Jenna
    Cui, Jiankun
    White, Andrew D.
    Bossy, Blaise
    Martinou, Jean-Claude
    Youle, Richard J.
    Lipton, Stuart A.
    Ellisman, Mark H.
    Perkins, Guy A.
    Bossy-Wetzel, Ella
    [J]. EMBO JOURNAL, 2006, 25 (16) : 3900 - 3911
  • [10] Resveratrol improves health and survival of mice on a high-calorie diet
    Baur, Joseph A.
    Pearson, Kevin J.
    Price, Nathan L.
    Jamieson, Hamish A.
    Lerin, Carles
    Kalra, Avash
    Prabhu, Vinayakumar V.
    Allard, Joanne S.
    Lopez-Lluch, Guillermo
    Lewis, Kaitlyn
    Pistell, Paul J.
    Poosala, Suresh
    Becker, Kevin G.
    Boss, Olivier
    Gwinn, Dana
    Wang, Mingyi
    Ramaswamy, Sharan
    Fishbein, Kenneth W.
    Spencer, Richard G.
    Lakatta, Edward G.
    Le Couteur, David
    Shaw, Reuben J.
    Navas, Placido
    Puigserver, Pere
    Ingram, Donald K.
    de Cabo, Rafael
    Sinclair, David A.
    [J]. NATURE, 2006, 444 (7117) : 337 - 342