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.
Keywords: AMPK; endothelial dysfunction; fusion/fission; metabolic memory; mitochondria dynamics.