The Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury

• Published in: Biomolecules (Basel, Switzerland) Vol. 11; no. 12; p. 1779
• Main Authors: Zheng, Yunsi, Luo, Anqi, Liu, Xiaoquan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.11.2021; MDPI
• Subjects: AMPK; Animals; Apoptosis; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Disease Models, Animal; endothelial dysfunction; fusion/fission; Glucose; Glucose - adverse effects; Homeostasis; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Kinases; Laboratory animals; Male; Membrane Potential, Mitochondrial - drug effects; metabolic memory; Metabolism; Mice; Mitochondria; Mitochondria - metabolism; mitochondria dynamics; Mitochondrial Dynamics; Penicillin; Phosphatase; Phosphorylation; Proteins; Reagents; Vascular System Injuries - etiology; Vascular System Injuries - metabolism; United States > US; China; AMPK; metabolic memory; mitochondria dynamics; endothelial dysfunction; fusion/fission
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11121779

Emerging evidence shows that mitochondria fusion/fission imbalance is related to the occurrence of hyperglycemia-induced vascular injury. To study the temporal dynamics of mitochondrial fusion and fission, we observed the alteration of mitochondrial fusion/fission proteins in a set of different high-glucose exposure durations, especially in the early stage of hyperglycemia. The in vitro results show that persistent cellular apoptosis and endothelial dysfunction can be induced rapidly within 12 hours’ high-glucose pre-incubation. Our results show that mitochondria maintain normal morphology and function within 4 hours’ high-glucose pre-incubation; with the extended high-glucose exposure, there is a transition to progressive fragmentation; once severe mitochondria fusion/fission imbalance occurs, persistent cellular apoptosis will develop. In vitro and in vivo results consistently suggest that mitochondrial fusion/fission homeostasis alterations trigger high-glucose-induced vascular injury. As the guardian of mitochondria, AMPK is suppressed in response to hyperglycemia, resulting in imbalanced mitochondrial fusion/fission, which can be reversed by AMPK stimulation. Our results suggest that mitochondrial fusion/fission’s staged homeostasis may be a predictive factor of diabetic cardiovascular complications.