Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2012, Article ID 703538, 11 pages
http://dx.doi.org/10.1155/2012/703538
Review Article

Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus

1Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
2Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA

Received 20 July 2011; Accepted 3 September 2011

Academic Editor: Sayon Roy

Copyright © 2012 Zhongmin Alex Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. L. Leahy, “Pathogenesis of type 2 diabetes mellitus,” Archives of Medical Research, vol. 36, no. 3, pp. 197–209, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. M. A. Permutt, J. Wasson, and N. Cox, “Genetic epidemiology of diabetes,” Journal of Clinical Investigation, vol. 115, no. 6, pp. 1431–1439, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Prentki and C. J. Nolan, “Islet beta cell failure in type 2 diabetes,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1802–1812, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. K. S. Polonsky, “Dynamics of insulin secretion in obesity and diabetes,” International Journal of Obesity and Related Metabolic Disorders, vol. 24, supplement 2, pp. S29–S31, 2000. View at Google Scholar
  5. D. Matthews, C. Cull, I. Stratton, R. R. Holman, and R. C. Turner, “UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK prospective diabetes study (UKPDS) group,” Diabetes Medicine, vol. 15, no. 4, pp. 945–950, 1998. View at Google Scholar
  6. A. E. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, R. A. Rizza, and P. C. Butler, “beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes,” Diabetes, vol. 52, no. 1, pp. 102–110, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Marchetti, R. Lupi, S. Del Guerra, M. Bugliani, L. Marselli, and U. Boggi, “The beta-cell in human type 2 diabetes,” Advances in Experimental Medicine and Biology, vol. 654, pp. 501–514, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. J. Fernandez-Alvarez, I. Conget, J. Rasschaert, A. Sener, R. Gomis, and W. J. Malaisse, “Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients,” Diabetologia, vol. 37, no. 2, pp. 177–181, 1994. View at Google Scholar · View at Scopus
  9. S. Deng, M. Vatamaniuk, X. Huang et al., “Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects,” Diabetes, vol. 53, no. 3, pp. 624–632, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Del Guerra, R. Lupi, L. Marselli et al., “Functional and molecular defects of pancreatic islets in human type 2 diabetes,” Diabetes, vol. 54, no. 3, pp. 727–735, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Anello, R. Lupi, D. Spampinato et al., “Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients,” Diabetologia, vol. 48, no. 2, pp. 282–289, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. K. Saito, T. Takahashi, N. Yaginuma, and N. Iwama, “Islet morphometry in the diabetic pancreas of man,” Tohoku Journal of Experimental Medicine, vol. 125, no. 2, pp. 185–197, 1978. View at Google Scholar · View at Scopus
  13. K. Saito, N. Yaginuma, and T. Takahashi, “Differential volumetry of A, B and D cells in the pancreatic islets of diabetic and nondiabetic subjects,” Tohoku Journal of Experimental Medicine, vol. 129, no. 3, pp. 273–283, 1979. View at Google Scholar · View at Scopus
  14. A. Clark, C. A. Wells, I. D. Buley et al., “Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes,” Diabetes Research, vol. 9, no. 4, pp. 151–159, 1988. View at Google Scholar · View at Scopus
  15. K. H. Yoon, S. H. Ko, J. H. Cho et al., “Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea,” The Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 5, pp. 2300–2308, 2003. View at Google Scholar
  16. A. Doria, M. E. Patti, and C. R. Kahn, “The emerging genetic architecture of type 2 diabetes,” Cell Metabolism, vol. 8, no. 3, pp. 186–200, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. G. C. Weir, D. R. Laybutt, H. Kaneto, S. Bonner-Weir, and A. Sharma, “Beta-cell adaptation and decompensation during the progression of diabetes,” Diabetes, vol. 50, supplement 1, pp. S154–S159, 2001. View at Google Scholar · View at Scopus
  18. M. Y. Donath and P. A. Halban, “Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications,” Diabetologia, vol. 47, no. 3, pp. 581–589, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. Z. Zhao, C. Zhao, H. Z. Xu et al., “Advanced glycation end products inhibit glucose-stimulated insulin secretion through nitric oxide-dependent inhibition of cytochrome c oxidase and adenosine triphosphate synthesis,” Endocrinology, vol. 150, no. 6, pp. 2569–2576, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. J. L. Leahy, I. B. Hirsch, and K. A. Peterson, “Targeting {beta}-cell function early in the course of therapy for type 2 Diabetes mellitus,” The Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 9, pp. 4206–4216, 2010. View at Google Scholar
  21. K. S. Polonsky and C. F. Semenkovich, “The pancreatic beta cell heats up: UCP2 and insulin secretion in diabetes,” Cell, vol. 105, no. 6, pp. 705–707, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Brownlee, “Biochemistry and molecular cell biology of diabetic complications,” Nature, vol. 414, no. 6865, pp. 813–820, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. P. Marchetti, S. Del Guerra, L. Marselli et al., “Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 11, pp. 5535–5541, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Y. Donath, J. A. Ehses, K. Maedler et al., “Mechanisms of {beta}-cell death in type 2 diabetes,” Diabetes, vol. 54, supplement 2, pp. S108–S113, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. A. P. Rolo and C. M. Palmeira, “Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress,” Toxicology and Applied Pharmacology, vol. 212, no. 2, pp. 167–178, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Friederich, P. Hansell, and F. Palm, “Diabetes, oxidative stress, nitric oxide and mitochondria function,” Current Diabetes Reviews, vol. 5, no. 2, pp. 120–144, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Zraika, R. L. Hull, J. Udayasankar et al., “Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis,” Diabetologia, vol. 52, no. 4, pp. 626–635, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. P. Maechler and C. B. Wollheim, “Mitochondrial function in normal and diabetic beta-cells,” Nature, vol. 414, no. 6865, pp. 807–812, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. M. W. Fariss, C. B. Chan, M. Patel, B. Van Houten, and S. Orrenius, “Role of mitochondria in toxic oxidative stress,” Molecular Interventions, vol. 5, no. 2, pp. 94–111, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. B. B. Lowell and G. I. Shulman, “Mitochondrial dysfunction and type 2 diabetes,” Science, vol. 307, no. 5708, pp. 384–387, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. F. F. Hsu and J. Turk, “Characterization of cardiolipin as the sodiated ions by positive-ion electrospray ionization with multiple stage quadrupole ion-trap mass spectrometry,” Journal of the American Society for Mass Spectrometry, vol. 17, no. 8, pp. 1146–1157, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. F. F. Hsu, J. Turk, E. R. Rhoades, D. G. Russell, Y. Shi, and E. A. Groisman, “Structural characterization of cardiolipin by tandem quadrupole and multiple-stage quadrupole ion-trap mass spectrometry with electrospray ionization,” Journal of the American Society for Mass Spectrometry, vol. 16, no. 4, pp. 491–504, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. X. Han, J. Yang, H. Cheng, K. Yang, D. R. Abendschein, and R. W. Gross, “Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction,” Biochemistry, vol. 44, no. 50, pp. 16684–16694, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. X. Han, J. Yang, K. Yang, Z. Zhongdan, D. R. Abendschein, and R. W. Gross, “Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: a shotgun lipidomics study,” Biochemistry, vol. 46, no. 21, pp. 6417–6428, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. A. C. Maritim, R. A. Sanders, and J. B. Watkins III, “Diabetes, oxidative stress, and antioxidants: a review,” Journal of Biochemical and Molecular Toxicology, vol. 17, no. 1, pp. 24–38, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Sakuraba, H. Mizukami, N. Yagihashi, R. Wada, C. Hanyu, and S. Yagihashi, “Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients,” Diabetologia, vol. 45, no. 1, pp. 85–96, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. A. P. Robertson, “Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes,” Journal of Biological Chemistry, vol. 279, no. 41, pp. 42351–42354, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. R. P. Robertson, J. Harmon, P. O. T. Tran, and V. Poitout, “Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes,” Diabetes, vol. 53, supplement 1, pp. S119–S124, 2004. View at Google Scholar · View at Scopus
  39. S. Furukawa, T. Fujita, M. Shimabukuro et al., “Increased oxidative stress in obesity and its impact on metabolic syndrome,” Journal of Clinical Investigation, vol. 114, no. 12, pp. 1752–1761, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. P. Jezek and L. Hlavata, “Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism,” The International Journal of Biochemistry and Cell Biology, vol. 37, no. 12, pp. 2478–2503, 2005. View at Google Scholar
  41. Q. Chen, E. J. Vazquez, S. Moghaddas, C. L. Hoppel, and E. J. Lesnefsky, “Production of reactive oxygen species by mitochondria: central role of complex III,” Journal of Biological Chemistry, vol. 278, no. 38, pp. 36027–36031, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. A. J. A. Molina, J. D. Wikstrom, L. Stiles et al., “Mitochondrial networking protects β-cells from nutrient-induced apoptosis,” Diabetes, vol. 58, no. 10, pp. 2303–2315, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. C. J. Rhodes, “Type 2 diabetes-a matter of beta-cell life and death?” Science, vol. 307, no. 5708, pp. 380–384, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Orrenius, “Mitochondrial regulation of apoptotic cell death,” Toxicology Letters, vol. 149, no. 1–3, pp. 19–23, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. X. Jiang and X. Wang, “Cytochrome C-mediated apoptosis,” Annual Review of Biochemistry, vol. 73, pp. 87–106, 2004. View at Google Scholar
  46. V. E. Kagan, V. A. Tyurin, J. Jiang et al., “Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors,” Nature Chemical Biology, vol. 1, no. 4, pp. 223–232, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Garrido, L. Galluzzi, M. Brunet, P. E. Puig, C. Didelot, and G. Kroemer, “Mechanisms of cytochrome c release from mitochondria,” Cell Death and Differentiation, vol. 13, no. 9, pp. 1423–1433, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. R. H. Houtkooper and F. M. Vaz, “Cardiolipin, the heart of mitochondrial metabolism,” Cellular and Molecular Life Sciences, vol. 65, no. 16, pp. 2493–2506, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Klingenberg, “Cardiolipin and mitochondrial carriers,” Biochimica et Biophysica Acta, vol. 1788, no. 10, pp. 2048–2058, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Orrenius and B. Zhivotovsky, “Cardiolipin oxidation sets cytochrome c free,” Nature Chemical Biology, vol. 1, no. 4, pp. 188–189, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Schlame, D. Rua, and M. L. Greenberg, “The biosynthesis and functional role of cardiolipin,” Progress in Lipid Research, vol. 39, no. 3, pp. 257–288, 2000. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Turk, B. A. Wolf, J. B. Lefkowith, W. T. Stumpa, and M. L. McDaniel, “Glucose-induced phospholipid hydrolysis in isolated pancreatic islets: quantitative effects on the phospholipid content of arachidonate and other fatty acids,” Biochimica et Biophysica Acta, vol. 879, no. 3, pp. 399–409, 1986. View at Google Scholar · View at Scopus
  53. F. H. Igney and P. H. Krammer, “Death and anti-death: tumour resistance to apoptosis,” Nature Reviews Cancer, vol. 2, no. 4, pp. 277–288, 2002. View at Google Scholar · View at Scopus
  54. M. Lutter, M. Fang, X. Luo, M. Nishijima, X. S. Xie, and X. Wang, “Cardiolipin provides specificity for targeting of tBid to mitochondria,” Nature Cell Biology, vol. 2, no. 10, pp. 754–756, 2000. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Li, C. Romestaing, X. Han et al., “Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity,” Cell Metabolism, vol. 12, no. 2, pp. 154–165, 2010. View at Publisher · View at Google Scholar
  56. M. E. Widlansky, J. Wang, S. M. Shenouda et al., “Altered mitochondrial membrane potential, mass, and morphology in the mononuclear cells of humans with type 2 diabetes,” Translational Research, vol. 156, no. 1, pp. 15–25, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. Z. Zhao, X. Zhang, C. Zhao et al., “Protection of pancreatic {beta}-cells by group VIA phospholipase A2-mediated repair of mitochondrial membrane peroxidation,” Endocrinology, vol. 151, no. 7, pp. 3038–3048, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. A. J. Chicco and G. C. Sparagna, “Role of cardiolipin alterations in mitochondrial dysfunction and disease,” American Journal of Physiology, vol. 292, no. 1, pp. C33–C44, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. F. Gonzalvez and E. Gottlieb, “Cardiolipin: setting the beat of apoptosis,” Apoptosis, vol. 12, no. 5, pp. 877–885, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. S. Pope, J. M. Land, and S. J. R. Heales, “Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target?” Biochimica et Biophysica Acta, vol. 1777, no. 7-8, pp. 794–799, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. I. Wiswedel, A. Gardemann, A. Storch, D. Peter, and L. Schild, “Degradation of phospholipids by oxidative stress—exceptional significance of cardiolipin,” Free Radical Research, vol. 44, no. 2, pp. 135–145, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. K. Seleznev, C. Zhao, X. H. Zhang, K. Song, and Z. A. Ma, “Calcium-independent phospholipase A2 localizes in and protects mitochondria during apoptotic induction by staurosporine,” Journal of Biological Chemistry, vol. 281, no. 31, pp. 22275–22288, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. F. M. Matschinsky, B. Glaser, and M. A. Magnuson, “Pancreatic beta-cell glucokinase: closing the gap between theoretical concepts and experimental realities,” Diabetes, vol. 47, no. 3, pp. 307–315, 1998. View at Publisher · View at Google Scholar · View at Scopus
  64. M. J. Macdonald and L. A. Fahien, “Insulin release in pancreatic islets by a glycolytic and a Krebs cycle intermediate: contrasting patterns of glyceraldehyde phosphate and succinate,” Archives of Biochemistry and Biophysics, vol. 279, no. 1, pp. 104–108, 1990. View at Publisher · View at Google Scholar · View at Scopus
  65. S. W. Ballinger, J. M. Shoffner, E. V. Hedaya et al., “Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondria DNA deletion,” Nature Genetics, vol. 1, no. 1, pp. 11–15, 1992. View at Google Scholar · View at Scopus
  66. H. Puccio, D. Simon, M. Cossee et al., “Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits,” Nature Genetics, vol. 27, no. 2, pp. 181–186, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. J. P. Silva, M. Kohler, C. Graff et al., “Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes,” Nature Genetics, vol. 26, no. 3, pp. 336–340, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. C. Y. Zhang, G. Baffy, P. Perret et al., “Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes,” Cell, vol. 105, no. 6, pp. 745–755, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. G. Patane, M. Anello, S. Piro, R. Vigneri, F. Purrello, and A. M. Rabuazzo, “Role of ATP production and uncoupling protein-2 in the insulin secretory defect induced by chronic exposure to high glucose or free fatty acids and effects of peroxisome proliferator-activated receptor-{gamma} inhibition,” Diabetes, vol. 51, no. 9, pp. 2749–2756, 2002. View at Google Scholar · View at Scopus
  70. K. S. Echtay, D. Roussel, J. St-Plerre et al., “Superoxide activates mitochondrial uncoupling proteins,” Nature, vol. 415, no. 6867, pp. 96–99, 2002. View at Publisher · View at Google Scholar · View at Scopus
  71. K. S. Echtay, M. P. Murphy, R. A. J. Smith, D. A. Talbot, and M. D. Brand, “Superoxide activates mitochondrial uncoupling protein 2 from the matrix side: studies using targeted antioxidants,” Journal of Biological Chemistry, vol. 277, no. 49, pp. 47129–47135, 2002. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Krauss, C.-Y. Zhang, L. Scorrano et al., “Superoxide-mediated activation of uncoupling protein 2 causes pancreatic {beta} cell dysfunction,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1831–1842, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. J. W. Joseph, V. Koshkin, M. C. Saleh et al., “Free fatty acid-induced {beta}-cell defects are dependent on uncoupling protein 2 expression,” Journal of Biological Chemistry, vol. 279, no. 49, pp. 51049–51056, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. C. T. De Souza, E. P. Araujo, L. F. Stoppiglia et al., “Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action,” FASEB Journal, vol. 21, no. 4, pp. 1153–1163, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. C. Y. Zhang, L. E. Parton, C. P. Ye et al., “Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets,” Cell Metabolism, vol. 3, no. 6, pp. 417–427, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. M. P. Murphy, K. S. Echtay, F. H. Blaikie et al., “Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria- targeted spin trap derived from alpha-phenyl-N-tert-butylnitrone,” Journal of Biological Chemistry, vol. 278, no. 49, pp. 48534–48545, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. M. D. Brand and T. C. Esteves, “Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3,” Cell Metabolism, vol. 2, no. 2, pp. 85–93, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. W. Liu, N. A. Porter, C. Schneider, A. R. Brash, and H. Yin, “Formation of 4-hydroxynonenal from cardiolipin oxidation: intramolecular peroxyl radical addition and decomposition,” Free Radical Biology and Medicine, vol. 50, no. 1, pp. 166–178, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Lenzen, J. Drinkgern, and M. Tiedge, “Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues,” Free Radical Biology and Medicine, vol. 20, no. 3, pp. 463–466, 1996. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Tiedge, S. Lortz, J. Drinkgern, and S. Lenzen, “Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells,” Diabetes, vol. 46, no. 11, pp. 1733–1742, 1997. View at Google Scholar · View at Scopus
  81. S. Lenzen, “Oxidative stress: the vulnerable beta-cell,” Biochemical Society Transactions, vol. 36, part 3, pp. 343–347, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. J. D. Acharya and S. S. Ghaskadbi, “Islets and their antioxidant defense,” Islets, vol. 2, no. 4, pp. 225–235, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. F. J. G. M. Van Kuijk, G. J. Handelman, and E. A. Dratz, “Consecutive action of phospholipase A2 and glutathione peroxidase is required for reduction of phospholipid hydroperoxides and provides a convenient method to determine peroxide values in membranes,” Journal of Free Radicals in Biology and Medicine, vol. 1, no. 5-6, pp. 421–427, 1985. View at Google Scholar · View at Scopus
  84. H. Imai and Y. Nakagawa, “Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells,” Free Radical Biology and Medicine, vol. 34, no. 2, pp. 145–169, 2003. View at Publisher · View at Google Scholar · View at Scopus
  85. Z. Ma and J. Turk, “The molecular biology of the group VIA Ca2+-independent phospholipase A2,” Progress in Nucleic Acid Research and Molecular Biology, vol. 67, pp. 1–33, 2001. View at Google Scholar · View at Scopus
  86. R. H. Schaloske and E. A. Dennis, “The phospholipase A2 superfamily and its group numbering system,” Biochimica et Biophysica Acta, vol. 1761, no. 11, pp. 1246–1259, 2006. View at Publisher · View at Google Scholar · View at Scopus
  87. D. A. Six and E. A. Dennis, “The expanding superfamily of phospholipase A2 enzymes: classification and characterization,” Biochimica et Biophysica Acta, vol. 1488, no. 1-2, pp. 1–19, 2000. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Sevanian, “Lipid damage and repair,” in Oxidative Damage and Repair, K. Davies, Ed., pp. 543–549, Pergamon Press, New York, NY, USA, 1988. View at Google Scholar
  89. A. Sevanian and P. Hochstein, “Mechanisms and consequences of lipid peroxidation in biological systems,” Annual Review of Nutrition, vol. 5, pp. 365–390, 1985. View at Google Scholar · View at Scopus
  90. S. Nigam and T. Schewe, “Phospholipase A2s and lipid peroxidation,” Biochimica et Biophysica Acta, vol. 1488, no. 1-2, pp. 167–181, 2000. View at Publisher · View at Google Scholar · View at Scopus
  91. D. K. Zachman, A. J. Chicco, S. A. Mccune, R. C. Murphy, R. L. Moore, and G. C. Sparagna, “The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the spontaneously hypertensive heart failure rat heart,” Journal of Lipid Research, vol. 51, no. 3, pp. 525–534, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. A. Malhotra, I. Edelman-Novemsky, Y. Xu et al., “Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 7, pp. 2337–2341, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. G. C. Sparagna and E. J. Lesnefsky, “Cardiolipin remodeling in the heart,” Journal of Cardiovascular Pharmacology, vol. 53, no. 4, pp. 290–301, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. G. M. Hatch, “Cell biology of cardiac mitochondrial phospholipids,” Biochemistry and Cell Biology, vol. 82, no. 1, pp. 99–112, 2004. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Bione, P. D'Adamo, E. Maestrini, A. K. Gedeon, P. A. Bolhuis, and D. Toniolo, “A novel X-linked gene, G4.5. is responsible for Barth syndrome,” Nature Genetics, vol. 12, no. 4, pp. 385–389, 1996. View at Publisher · View at Google Scholar · View at Scopus
  96. A. F. Neuwald, “Barth syndrome may be due to an acyltransferase deficiency,” Current Biology, vol. 7, no. 8, pp. R465–R466, 1997. View at Google Scholar · View at Scopus
  97. Y. Xu, A. Malhotra, M. Ren, and M. Schlame, “The enzymatic function of tafazzin,” Journal of Biological Chemistry, vol. 281, no. 51, pp. 39217–39224, 2006. View at Publisher · View at Google Scholar · View at Scopus
  98. N. V. Morgan, S. K. Westaway, J. E. V. Morton et al., “PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron,” Nature Genetics, vol. 38, no. 7, pp. 752–754, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. I. Malik, J. Turk, D. J. Mancuso et al., “Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations,” American Journal of Pathology, vol. 172, no. 2, pp. 406–416, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Cai and D. P. Jones, “Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss,” Journal of Biological Chemistry, vol. 273, no. 19, pp. 11401–11404, 1998. View at Publisher · View at Google Scholar · View at Scopus
  101. A. V. Matveyenko and P. C. Butler, “Relationship between beta-cell mass and diabetes onset,” Diabetes, Obesity and Metabolism, vol. 10, supplement 4, pp. 23–31, 2008. View at Google Scholar
  102. K. Song, X. Zhang, C. Zhao, N. T. Ang, and Z. A. Ma, “Inhibition of Ca2+-independent phospholipase A2 results in insufficient insulin secretion and impaired glucose tolerance,” Molecular Endocrinology, vol. 19, no. 2, pp. 504–515, 2005. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Bao, D. J. Miller, Z. Ma et al., “Male mice that do not express group VIA phospholipase A2 produce spermatozoa with impaired motility and have greatly reduced fertility,” Journal of Biological Chemistry, vol. 279, no. 37, pp. 38194–38200, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. K. Shinzawa, H. Sumi, M. Ikawa et al., “Neuroaxonal dystrophy caused by group VIA phospholipase A2 deficiency in mice: a model of human neurodegenerative disease,” Journal of Neuroscience, vol. 28, no. 9, pp. 2212–2220, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Ramanadham, H. Song, S. Bao et al., “Islet complex lipids: involvement in the actions of group VIA calcium-independent phospholipase A2 in beta-cells,” Diabetes, vol. 53, no. 90001, pp. S179–S185, 2004. View at Google Scholar
  106. J. M. Moran, R. M. L. Buller, J. McHowat et al., “Genetic and pharmacologic evidence that calcium-independent phospholipase A2{beta} regulates virus-induced inducible nitric-oxide synthase expression by macrophages,” Journal of Biological Chemistry, vol. 280, no. 30, pp. 28162–28168, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. S. Bao, Y. Li, X. Lei et al., “Attenuated free cholesterol loading-induced apoptosis but preserved phospholipid composition of peritoneal macrophages from mice that do not express group VIA phospholipase A2,” Journal of Biological Chemistry, vol. 282, no. 37, pp. 27100–27114, 2007. View at Publisher · View at Google Scholar · View at Scopus
  108. D. A. Jacobson, C. R. Weber, S. Bao, J. Turk, and L. H. Philipson, “Modulation of the pancreatic islet beta-cell-delayed rectifier potassium channel Kv2.1 by the polyunsaturated fatty acid arachidonate,” Journal of Biological Chemistry, vol. 282, no. 10, pp. 7442–7449, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. Z. Xie, M. C. Gong, W. Su, J. Turk, and Z. Guo, “Group VIA phospholipase A2 (iPLA2beta) participates in angiotensin II-induced transcriptional up-regulation of regulator of G-protein signaling-2 in vascular smooth muscle cells,” Journal of Biological Chemistry, vol. 282, no. 35, pp. 25278–25289, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. M. J. Carper, S. Zhang, J. Turk, and S. Ramanadham, “Skeletal muscle group VIA phospholipase A2 (iPLA2beta): expression and role in fatty acid oxidation,” Biochemistry, vol. 47, no. 46, pp. 12241–12249, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. H. M. Sung, C. M. Jenkins, D. J. Mancuso, J. Turk, and R. W. Gross, “Smooth muscle cell arachidonic acid release, migration, and proliferation are markedly attenuated in mice null for calcium-independent phospholipase A2beta,” Journal of Biological Chemistry, vol. 283, no. 49, pp. 33975–33987, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. S. Ramanadham, K. E. Yarasheski, M. J. Silva et al., “Age-related changes in bone morphology are accelerated in group VIA phospholipase A2 (iPLA2{beta})-null mice,” American Journal of Pathology, vol. 172, no. 4, pp. 868–881, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. H. H. Dietrich, D. R. Abendschein, S. H. Moon et al., “Genetic ablation of calcium-independent phospholipase A2{beta} causes hypercontractility and markedly attenuates endothelium-dependent relaxation to acetylcholine,” American Journal of Physiology, vol. 298, no. 6, pp. H2208–H2220, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. S. Bao, H. Song, M. Wohltmann et al., “Insulin secretory responses and phospholipid composition of pancreatic islets from mice that do not express group VIA phospholipase A2 and effects of metabolic stress on glucose homeostasis,” Journal of Biological Chemistry, vol. 281, no. 30, pp. 20958–20973, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. S. Bao, D. A. Jacobson, and M. Wohltmann, “Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2{beta} in pancreatic {beta}-cells and in iPLA2{beta}-null mice,” American Journal of Physiology, vol. 294, no. 2, pp. E217–E229, 2008. View at Google Scholar
  116. M. Zhang, E. Mileykovskaya, and W. Dowhan, “Cardiolipin is essential for organization of complexes III and IV into a supercomplex in intact yeast mitochondria,” Journal of Biological Chemistry, vol. 280, no. 33, pp. 29403–29408, 2005. View at Publisher · View at Google Scholar · View at Scopus
  117. V. M. Gohil, P. Hayes, S. Matsuyama, H. Schägger, M. Schlame, and M. L. Greenberg, “Cardiolipin biosynthesis and mitochondrial respiratory chain function are interdependent,” Journal of Biological Chemistry, vol. 279, no. 41, pp. 42612–42618, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. V. M. Gohil and M. L. Greenberg, “Mitochondrial membrane biogenesis: phospholipids and proteins go hand in hand,” Journal of Cell Biology, vol. 184, no. 4, pp. 469–472, 2009. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Orrenius, V. Gogvadze, and B. Zhivotovsky, “Mitochondrial oxidative stress: implications for cell death,” Annual Review of Pharmacology and Toxicology, vol. 47, pp. 143–183, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. G. Petrosillo, G. Colantuono, N. Moro et al., “Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening,” American Journal of Physiology, vol. 297, no. 4, pp. H1487–H1493, 2009. View at Publisher · View at Google Scholar · View at Scopus
  121. S. Subramanian, B. Kalyanaraman, and R. Q. Migrino, “Mitochondrially targeted antioxidants for the treatment of cardiovascular diseases,” Recent Patents on Cardiovascular Drug Discovery, vol. 5, no. 1, pp. 54–65, 2010. View at Google Scholar
  122. A. Dhanasekaran, S. Kotamraju, S. V. Kalivendi et al., “Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis,” Journal of Biological Chemistry, vol. 279, no. 36, pp. 37575–37587, 2004. View at Publisher · View at Google Scholar · View at Scopus
  123. G. Petrosillo, N. Moro, F. M. Ruggiero, and G. Paradies, “Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release,” Free Radical Biology and Medicine, vol. 47, no. 7, pp. 969–974, 2009. View at Publisher · View at Google Scholar · View at Scopus