Mitochondria undergo repeated cycles of fusion and fission that regulate their size and shape by a process known as mitochondrial dynamics. Numerous studies have revealed the importance of this process in maintaining mitochondrial health and cellular homeostasis, particularly in highly metabolically active tissues such as skeletal muscle and the heart. Here, we review the literature on the relationship between mitochondrial dynamics and the pathophysiology of type 2 diabetes and cardiovascular disease (CVD). Importantly, we emphasize divergent outcomes resulting from downregulating distinct mitochondrial dynamics proteins in various tissues. This review underscores compensatory mechanisms and adaptive pathways that offset potentially detrimental effects, resulting instead in improved metabolic health. Finally, we offer a perspective on potential therapeutic implications of modulating mitochondrial dynamics proteins for treatment of diabetes and CVD.
Article Highlights
- Changes in mitochondrial dynamics favoring a more fragmented morphology have been associated with the pathophysiology of insulin resistance, diabetes, and cardiovascular diseases.
- Studies in transgenic animal models established a causal link between manipulating different mitochondrial dynamics proteins and development of cardiometabolic dysregulation.
- Deletion of mitochondrial dynamics proteins in some tissues may lead to activation of adaptive stress response pathways, resulting in improved systemic metabolic health.
- Interventions aiming at restoring mitochondrial fission and fusion balance in a tissue-specific manner may be beneficial in the context of metabolic and cardiovascular diseases.
