Journal
BIOMOLECULES
Volume 11, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/biom11121779
Keywords
endothelial dysfunction; mitochondria dynamics; fusion; fission; metabolic memory; AMPK
Categories
Funding
- Natural Science Foundation of China [81773806, 81903703]
- Double First-Class University project [CPU2018GY19]
- Fundamental Research Funds for the Central Universities [2632018ZD10]
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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.
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.
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