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

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.

Automated summary

Prolonged exposure to high glucose leads to mitochondrial fragmentation, triggering cell apoptosis and vascular injury. AMPK is suppressed by high glucose, causing imbalanced mitochondrial fusion/fission, which can be reversed with AMPK stimulation, serving as a predictive factor for diabetic cardiovascular complications.