A Review of Mitochondrial Dysfunction as a Central Mechanism in Metabolic Diseases
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The mitochondrial dysfunction has become an important biological mechanism underlying the development and progression of metabolic diseases. Mitochondria are key in the generation of cellular energy, glucose and lipid metabolism, redox control and metabolic homeostasis. Disruption of mitochondrial biogenesis, dynamics, oxidative phosphorylation, and quality-control mechanisms can contribute to the production of increased reactive oxygen species, disturbance of cellular energy metabolism, and metabolic disturbances. There is emerging evidence that mitochondrial dysfunction is related to insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease and cardiometabolic complications. Furthermore, dysfunctional mitochondria have close interactions with inflammatory pathways, which are related to chronic low-grade inflammation, leading to a vicious cycle of further metabolic dysfunction. Recovering mitochondrial function is a therapeutic target for lifestyle modification, physical exercise, pharmacological, antioxidant and emerging mitochondrial targeted therapies. Regulation of mitochondrial biogenesis, dynamics, mitophagy, and redox signaling are of particular interest as therapeutic targets. While there is encouraging research and clinical data, there is still a need for more studies to determine the long-term efficacy and safety of mitochondria-targeted interventions. The aim of this review is to summarize the current available evidence regarding mitochondrial dysfunction as a central mechanism in metabolic diseases and focus on the molecular mechanisms, role in the main metabolic diseases, interactions with inflammatory processes and metabolic homeostasis and therapeutic potential.
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