Journal of Medicine and Life Science

Institute for Medical Science (제주대학교 의과학연구소)
권호 표지
DOI QR코드

DOI QR Code

Mitochondrial fatty acid metabolism in acute kidney injury

  • Jang, Hee-Seong (Department of Cellular and Integrative Physiology, University of Nebraska Medical Center) ;
  • Padanilam, Babu J. (Department of Cellular and Integrative Physiology, University of Nebraska Medical Center)
  • Received : 2018.09.01
  • Accepted : 2018.10.07
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Mitochondrial injury in renal tubule has been recognized as a major contributor in acute kidney injury (AKI) pathogenesis. Ischemic insult, nephrotoxin, endotoxin and contrast medium destroy mitochondrial structure and function as well as their biogenesis and dynamics, especially in renal proximal tubule, to elicit ATP depletion. Mitochondrial fatty acid ${\beta}$-oxidation (FAO) is the preferred source of ATP in the kidney, and its impairment is a critical factor in AKI pathogenesis. This review explores current knowledge of mitochondrial dysfunction and energy depletion in AKI and prospective views on developing therapeutic strategies targeting mitochondrial dysfunction in AKI.

Keywords

References

  1. Eltzschig HK, Eckle T. Ischemia and reperfusion - from mechanism to translation. Nat Med 2011;17:1391-401. https://doi.org/10.1038/nm.2507
  2. Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest 2004;114:5-14. https://doi.org/10.1172/JCI200422353
  3. Case J, Khan S, Khalid R, Khan A. Epidemiology of acute kidney injury in the intensive care unit. Crit Care Res Pract 2013; 2013:479730.
  4. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012;81:442-8. https://doi.org/10.1038/ki.2011.379
  5. He L, Wei Q, Liu J, Yi M, Liu Y, Liu H, et al. AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms. Kidney Int 2017;92:1071-83. https://doi.org/10.1016/j.kint.2017.06.030
  6. Basile DP, Bonventre JV, Mehta R, Nangaku M, Unwin R, Rosner MH, et al. Progression after AKI: Understanding Maladaptive Repair Processes to Predict and Identify Therapeutic Treatments. J Am Soc Nephrol 2016;27:687-97. https://doi.org/10.1681/ASN.2015030309
  7. Molitoris BA. Therapeutic translation in acute kidney injury: the epithelial/endothelial axis. J Clin Invest 2014;124:2355-63. https://doi.org/10.1172/JCI72269
  8. Agarwal A, Dong Z, Harris R, Murray P, Parikh SM, Rosner MH, et al. Cellular and Molecular Mechanisms of AKI. J Am Soc Nephrol 2016;27: 1288-99. https://doi.org/10.1681/ASN.2015070740
  9. Weinberg JM, Venkatachalam MA, Roeser NF, Saikumar P, Dong Z, Senter RA, et al. Anaerobic and aerobic pathways for salvage of proximal tubules from hypoxia-induced mitochondrial injury. Am J Physiol Renal Physiol 2000;279:F927-43. https://doi.org/10.1152/ajprenal.2000.279.5.F927
  10. Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol 2012;2:1303-53.
  11. Nourbakhsh N, Singh P. Role of renal oxygenation and mitochondrial function in the pathophysiology of acute kidney injury. Nephron Clin Pract 2014;127:149-52. https://doi.org/10.1159/000363545
  12. Bhargava P, Schnellmann RG. Mitochondrial energetics in the kidney. Nat Rev Nephrol 2017;13:629-46. https://doi.org/10.1038/nrneph.2017.107
  13. Stallons LJ, Funk JA, Schnellmann RG. Mitochondrial Homeostasis in Acute Organ Failure. Curr Pathobiol Rep 2013;1:10.
  14. Hall AM, Schuh CD. Mitochondria as therapeutic targets in acute kidney injury. Curr Opin Nephrol Hypertens 2016;25:355-62. https://doi.org/10.1097/MNH.0000000000000228
  15. Forbes JM. Mitochondria-Power Players in Kidney Function? Trends Endocrinol Metab 2016;27:441-2. https://doi.org/10.1016/j.tem.2016.05.002
  16. Chandel NS. Evolution of Mitochondria as Signaling Organelles. Cell Metab 2015;22:204-6. https://doi.org/10.1016/j.cmet.2015.05.013
  17. Mandel LJ. Primary active sodium transport, oxygen consumption, and ATP: coupling and regulation. Kidney Int 1986;29:3-9. https://doi.org/10.1038/ki.1986.2
  18. Simon N, Hertig A. Alteration of Fatty Acid Oxidation in Tubular Epithelial Cells: From Acute Kidney Injury to Renal Fibrogenesis. Front Med (Lausanne) 2015;2:52.
  19. Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 2011;121:4210-21. https://doi.org/10.1172/JCI45161
  20. Szeto HH. Pharmacologic Approaches to Improve Mitochondrial Function in AKI and CKD. J Am Soc Nephrol 2017;28:2856-65. https://doi.org/10.1681/ASN.2017030247
  21. Aon MA, Bhatt N, Cortassa SC. Mitochondrial and cellular mechanisms for managing lipid excess. Front Physiol 2014;5:282.
  22. Idrovo JP, Yang WL, Nicastro J, Coppa GF, Wang P. Stimulation of carnitine palmitoyltransferase 1 improves renal function and attenuates tissue damage after ischemia/reperfusion. J Surg Res 2012;177:157-64. https://doi.org/10.1016/j.jss.2012.05.053
  23. Portilla D. Role of fatty acid beta-oxidation and calcium-independent phospholipase A2 in ischemic acute renal failure. Curr Opin Nephrol Hypertens 1999;8:473-7. https://doi.org/10.1097/00041552-199907000-00012
  24. Bobulescu IA. Renal lipid metabolism and lipotoxicity. Curr Opin Nephrol Hypertens 2010;19:393-402. https://doi.org/10.1097/MNH.0b013e32833aa4ac
  25. Weinberg JM. Lipotoxicity. Kidney Int 2006;70:1560-6. https://doi.org/10.1038/sj.ki.5001834
  26. Zager RA, Johnson AC, Hanson SY. Renal tubular triglyercide accumulation following endotoxic, toxic, and ischemic injury. Kidney Int 2005;67:111-21. https://doi.org/10.1111/j.1523-1755.2005.00061.x
  27. Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A 2003;100:3077-82. https://doi.org/10.1073/pnas.0630588100
  28. Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med 2015;21:37-46. https://doi.org/10.1038/nm.3762
  29. Tran M, Parikh SM. Mitochondrial biogenesis in the acutely injured kidney. Nephron Clin Pract 2014;127:42-5. https://doi.org/10.1159/000363715
  30. Weinberg JM. Mitochondrial biogenesis in kidney disease. J Am Soc Nephrol 2011;22:431-6. https://doi.org/10.1681/ASN.2010060643
  31. Portilla D. Energy metabolism and cytotoxicity. Semin Nephrol 2003;23:432-8. https://doi.org/10.1016/S0270-9295(03)00088-3
  32. Portilla D, Dai G, McClure T, Bates L, Kurten R, Megyesi J, et al. Alterations of PPARalpha and its coactivator PGC-1 in cisplatin-induced acute renal failure. Kidney Int 2002;62:1208-18. https://doi.org/10.1111/j.1523-1755.2002.kid553.x
  33. Portilla D, Dai G, Peters JM, Gonzalez FJ, Crew MD, Proia AD. Etomoxir-induced PPARalpha-modulated enzymes protect during acute renal failure. Am J Physiol Renal Physiol 2000;278:F667-75. https://doi.org/10.1152/ajprenal.2000.278.4.F667
  34. Portilla D, Li S, Nagothu KK, Megyesi J, Kaissling B, Schnackenberg L, et al. Metabolomic study of cisplatin-induced nephrotoxicity. Kidney Int 2006;69:2194-204. https://doi.org/10.1038/sj.ki.5000433
  35. Nagothu KK, Bhatt R, Kaushal GP, Portilla D. Fibrate prevents cisplatin-induced proximal tubule cell death. Kidney Int 2005;68:2680-93. https://doi.org/10.1111/j.1523-1755.2005.00739.x
  36. Li S, Wu P, Yarlagadda P, Vadjunec NM, Proia AD, Harris RA, et al. PPAR alpha ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity. Am J Physiol Renal Physiol 2004;286:F572-80. https://doi.org/10.1152/ajprenal.00190.2003
  37. Kamijo Y, Hora K, Kono K, Takahashi K, Higuchi M, Ehara T, et al. PPARalpha protects proximal tubular cells from acute fatty acid toxicity. J Am Soc Nephrol 2007;18:3089-100. https://doi.org/10.1681/ASN.2007020238
  38. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849-61. https://doi.org/10.1016/S0140-6736(05)67667-2
  39. Cases A, Coll E. Dyslipidemia and the progression of renal disease in chronic renal failure patients. Kidney Int Suppl 2005:S87-93.
  40. Idrovo JP, Yang WL, Matsuda A, Nicastro J, Coppa GF, Wang P. Post-treatment with the combination of 5-aminoimidazole-4-carboxyamide ribonucleoside and carnitine improves renal function after ischemia/reperfusion injury. Shock 2012;37:39-46. https://doi.org/10.1097/SHK.0b013e31823185d7
  41. Mister M, Noris M, Szymczuk J, Azzollini N, Aiello S, Abbate M, et al. Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion. Kidney Int 2002;61:1064-78. https://doi.org/10.1046/j.1523-1755.2002.00212.x