Targeting Mitochondrial Reactive Oxygen Species As Novel Therapy for Inflammatory Diseases and Cancers

Overview

Journal J Hematol Oncol

Publisher Biomed Central

Specialties Hematology
Oncology

Date 2013 Feb 28

PMID 23442817

Citations 332

Authors

Xinyuan Li

Pu Fang

Jietang Mai

Eric T Choi

Hong Wang

Xiao-Feng Yang

Affiliations

Soon will be listed here.

Abstract

There are multiple sources of reactive oxygen species (ROS) in the cell. As a major site of ROS production, mitochondria have drawn considerable interest because it was recently discovered that mitochondrial ROS (mtROS) directly stimulate the production of proinflammatory cytokines and pathological conditions as diverse as malignancies, autoimmune diseases, and cardiovascular diseases all share common phenotype of increased mtROS production above basal levels. Several excellent reviews on this topic have been published, but ever-changing new discoveries mandated a more up-to-date and comprehensive review on this topic. Therefore, we update recent understanding of how mitochondria generate and regulate the production of mtROS and the function of mtROS both in physiological and pathological conditions. In addition, we describe newly developed methods to probe or scavenge mtROS and compare these methods in detail. Thorough understanding of this topic and the application of mtROS-targeting drugs in the research is significant towards development of better therapies to combat inflammatory diseases and inflammatory malignancies.

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References

Xie H, Lev D, Gong Y, Wang S, Pollock R, Wu X . Reduced mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of soft tissue sarcoma. Carcinogenesis. 2013; 34(5):1039-43. DOI: 10.1093/carcin/bgt023. View

Schriner S, Linford N, Martin G, Treuting P, Ogburn C, Emond M . Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005; 308(5730):1909-11. DOI: 10.1126/science.1106653. View

Graham D, Huynh N, Hamilton C, Beattie E, Smith R, Cocheme H . Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. Hypertension. 2009; 54(2):322-8. DOI: 10.1161/HYPERTENSIONAHA.109.130351. View

Dickinson B, Srikun D, Chang C . Mitochondrial-targeted fluorescent probes for reactive oxygen species. Curr Opin Chem Biol. 2009; 14(1):50-6. PMC: 2830890. DOI: 10.1016/j.cbpa.2009.10.014. View

Bailey S, Mitra S, Flavahan S, Flavahan N . Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries. Am J Physiol Heart Circ Physiol. 2005; 289(1):H243-50. DOI: 10.1152/ajpheart.01305.2004. View

Smith R, Porteous C, Coulter C, Murphy M . Selective targeting of an antioxidant to mitochondria. Eur J Biochem. 1999; 263(3):709-16. DOI: 10.1046/j.1432-1327.1999.00543.x. View

Doughan A, Harrison D, Dikalov S . Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res. 2007; 102(4):488-96. DOI: 10.1161/CIRCRESAHA.107.162800. View

Zheng Z, Chen H, Wang H, Ke B, Zheng B, Li Q . Improvement of retinal vascular injury in diabetic rats by statins is associated with the inhibition of mitochondrial reactive oxygen species pathway mediated by peroxisome proliferator-activated receptor gamma coactivator 1alpha. Diabetes. 2010; 59(9):2315-25. PMC: 2927955. DOI: 10.2337/db10-0638. View

Tedgui A, Mallat Z . Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006; 86(2):515-81. DOI: 10.1152/physrev.00024.2005. View

10.

Gerthoffer W . Mechanisms of vascular smooth muscle cell migration. Circ Res. 2007; 100(5):607-21. DOI: 10.1161/01.RES.0000258492.96097.47. View

11.

Yamagishi S, Edelstein D, Du X, Kaneda Y, Guzman M, Brownlee M . Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem. 2001; 276(27):25096-100. DOI: 10.1074/jbc.M007383200. View

12.

Lavoie J, Sigmund C . Minireview: overview of the renin-angiotensin system--an endocrine and paracrine system. Endocrinology. 2003; 144(6):2179-83. DOI: 10.1210/en.2003-0150. View

13.

Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto J, Bagi Z, Ballabh P . Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol. 2009; 297(5):H1876-81. PMC: 2781360. DOI: 10.1152/ajpheart.00375.2009. View

14.

Strowig T, Henao-Mejia J, Elinav E, Flavell R . Inflammasomes in health and disease. Nature. 2012; 481(7381):278-86. DOI: 10.1038/nature10759. View

15.

Davidson S . Endothelial mitochondria and heart disease. Cardiovasc Res. 2010; 88(1):58-66. DOI: 10.1093/cvr/cvq195. View

16.

Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R . Endothelial-specific expression of mitochondrial thioredoxin improves endothelial cell function and reduces atherosclerotic lesions. Am J Pathol. 2007; 170(3):1108-20. PMC: 1864879. DOI: 10.2353/ajpath.2007.060960. View

17.

Gross O, Thomas C, Guarda G, Tschopp J . The inflammasome: an integrated view. Immunol Rev. 2011; 243(1):136-51. DOI: 10.1111/j.1600-065X.2011.01046.x. View

18.

Weber C, Noels H . Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011; 17(11):1410-22. DOI: 10.1038/nm.2538. View

19.

Widder J, Fraccarollo D, Galuppo P, Hansen J, Jones D, Ertl G . Attenuation of angiotensin II-induced vascular dysfunction and hypertension by overexpression of Thioredoxin 2. Hypertension. 2009; 54(2):338-44. PMC: 2752391. DOI: 10.1161/HYPERTENSIONAHA.108.127928. View

20.

Howitz K, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J . Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425(6954):191-6. DOI: 10.1038/nature01960. View