Glycoxidative stress-induced mitophagy modulates mitochondrial fates.
Diabetes mellitus (DM), a state of chronic hyperglycemia, is associated with a variety of serious complications. Hyperglycemia-induced advanced glycation end products (AGEs) play an important role in the development of diabetic complications. In vivo, we demonstrated that disrupted mitochondria and autophagy was elevated in type II DM db/db mice. Mitophagy was evidenced by increased autophagosome formation in the beta-islet cells. The adducts of N(epsilon)-(carboxymethyl) lysine (CML), a major AGE, and bovine serum albumin (CML-BSA) stimulated the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II in rat insulinoma cells (RIN-m5F). CML-BSA increased ROS generation as demonstrated in a time-dependent manner. Experiments with mitochondrial targeted enhanced yellow fluorescent protein transfected RIN-m5F cells, massive fragmented mitochondria were visualized in the CML-BSA treated cells. Taken together, these data suggested that AGEs may cause mitochondrial dysfunction and mitophagosome formation, and AGEs-induced glycoxidative stress may trigger mitophagic process to modulate mitochondrial fates leading to either cell survival or cell death.
Lo
Mei-Chen
MC
Graduate Institute of Medical Sciences, School of Medical Laboratory Sciences and Biotechnology, College of Medicine, Taipei Medical University, Taipei, [corrected] Taiwan.
Lu
Chin-I
CI
Chen
Ming-Hong
MH
Chen
Chun-Da
CD
Lee
Horng-Mo
HM
Kao
Shu-Huei
SH
D000818:Animals; D002417:Cattle; D016923:Cell Death; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006943:Hyperglycemia; D007340:Insulinoma / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress; D010588:Phagosomes / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D012709:Serum Albumin / Q000737:chemistry
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D012709:Serum Albumin; C048496:N(6)-carboxymethyllysine; D008239:Lysine