Melatonin Affects Mitochondrial Fission/Fusion Dynamics in the Diabetic Retina. (11th April 2019)

• Record Type: Journal Article
• Authors: Chang, Janet Ya-An; Yu, Fei; Shi, Liheng; Ko, Michael L.; Ko, Gladys Y.-P.
• Other Names: Simó Rafael Guest Editor.
• Is Part Of: Journal of diabetes research. Volume 2019(2019)
• Publication Date: 2019-04-11
• Subjects: Diabetes -- Periodicals; Diabetes -- Pathophysiology -- Periodicals; Diabetes -- Prevention -- Periodicals; Diabetes -- Etiology -- Periodicals; Diabetes -- Epidemiology -- Periodicals; Diabetes -- Pathogenesis -- Periodicals; 616.462005
• DOI: 10.1155/2019/8463125
• Languages: English
• ISSNs: 2314-6745

Abstract

Abstract : Mitochondrial fission and fusion are dependent on cellular nutritional states, and maintaining this dynamics is critical for the health of cells. Starvation triggers mitochondrial fusion to maintain bioenergetic efficiency, but during nutrient overloads (as with hyperglycemic conditions), fragmenting mitochondria is a way to store nutrients to avoid waste of energy. In addition to ATP production, mitochondria play an important role in buffering intracellular calcium (Ca 2+ ). We found that in cultured 661W cells, a photoreceptor-derived cell line, hyperglycemic conditions triggered an increase of the expression of dynamin-related protein 1 (DRP1), a protein marker of mitochondrial fission, and a decrease of mitofusin 2 (MFN2), a protein for mitochondrial fusion. Further, these hyperglycemic cells also had decreased mitochondrial Ca 2+ but increased cytosolic Ca 2+ . Treating these hyperglycemic cells with melatonin, a multifaceted antioxidant, averted hyperglycemia-altered mitochondrial fission-and-fusion dynamics and mitochondrial Ca 2+ levels. To mimic how people most commonly take melatonin supplements, we gave melatonin to streptozotocin- (STZ-) induced type 1 diabetic mice by daily oral gavage and determined the effects of melatonin on diabetic eyes. We found that melatonin was not able to reverse the STZ-induced systemic hyperglycemic condition, but it prevented STZ-induced damage to the neural retina and retinal microvasculature. The beneficial effects of melatonin in the neural retina in part were through alleviating STZ-caused changes in mitochondrial dynamics and Ca 2+ buffering.