2024 | Luis Miguel García-Peña, E. Dale Abel, and Renata O. Pereira
The article "Mitochondrial Dynamics, Diabetes, and Cardiovascular Disease" by Luis Miguel García-Peña, E. Dale Abel, and Renata O. Perreira reviews the role of mitochondrial dynamics in the pathophysiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Mitochondrial dynamics, which involve the fusion and fission of mitochondria, are crucial for maintaining mitochondrial health and cellular homeostasis. The review highlights how alterations in these processes can lead to mitochondrial dysfunction, increased reactive oxygen species (ROS) production, impaired fatty acid oxidation, and reduced energy expenditure, contributing to insulin resistance (IR) and metabolic disorders.
In T2D, dysfunctional mitochondria characterized by reduced bioenergetic responses to insulin stimulation and decreased mitochondrial biogenesis are common. Studies have shown that changes in the expression levels of mitochondrial dynamics proteins, such as mitofusin 1 and 2 (MFN1/2) and optic atrophy 1 (OPA1), can contribute to IR and metabolic disorders. For example, reduced MFN2 levels correlate with skeletal muscle IR, while increased MFN2 levels are observed following weight loss. OPA1 protein expression is also reduced in skeletal muscle from individuals with obesity and T2D.
The review also discusses the impact of mitochondrial dynamics on CVD, including heart failure (HF), diabetic cardiomyopathy, and atherosclerosis. Excessive mitochondrial fission, often due to posttranslational modifications of dynamin-related protein 1 (DRP1) or reduced levels of fusion proteins, can lead to mitochondrial fragmentation and impaired bioenergetics. This can result in increased ROS production, mtDNA damage, and impaired cell survival, contributing to the progression of CVD.
Finally, the article explores potential therapeutic implications of modulating mitochondrial dynamics proteins for the treatment of metabolic disorders and CVD. While pharmacological approaches targeting these proteins show promise, they must be carefully considered due to potential side effects and tissue-specific responses. The review emphasizes the need for further research to understand the complex interactions between mitochondrial dynamics and disease, as well as the development of targeted therapies that can safely modulate these processes.The article "Mitochondrial Dynamics, Diabetes, and Cardiovascular Disease" by Luis Miguel García-Peña, E. Dale Abel, and Renata O. Perreira reviews the role of mitochondrial dynamics in the pathophysiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Mitochondrial dynamics, which involve the fusion and fission of mitochondria, are crucial for maintaining mitochondrial health and cellular homeostasis. The review highlights how alterations in these processes can lead to mitochondrial dysfunction, increased reactive oxygen species (ROS) production, impaired fatty acid oxidation, and reduced energy expenditure, contributing to insulin resistance (IR) and metabolic disorders.
In T2D, dysfunctional mitochondria characterized by reduced bioenergetic responses to insulin stimulation and decreased mitochondrial biogenesis are common. Studies have shown that changes in the expression levels of mitochondrial dynamics proteins, such as mitofusin 1 and 2 (MFN1/2) and optic atrophy 1 (OPA1), can contribute to IR and metabolic disorders. For example, reduced MFN2 levels correlate with skeletal muscle IR, while increased MFN2 levels are observed following weight loss. OPA1 protein expression is also reduced in skeletal muscle from individuals with obesity and T2D.
The review also discusses the impact of mitochondrial dynamics on CVD, including heart failure (HF), diabetic cardiomyopathy, and atherosclerosis. Excessive mitochondrial fission, often due to posttranslational modifications of dynamin-related protein 1 (DRP1) or reduced levels of fusion proteins, can lead to mitochondrial fragmentation and impaired bioenergetics. This can result in increased ROS production, mtDNA damage, and impaired cell survival, contributing to the progression of CVD.
Finally, the article explores potential therapeutic implications of modulating mitochondrial dynamics proteins for the treatment of metabolic disorders and CVD. While pharmacological approaches targeting these proteins show promise, they must be carefully considered due to potential side effects and tissue-specific responses. The review emphasizes the need for further research to understand the complex interactions between mitochondrial dynamics and disease, as well as the development of targeted therapies that can safely modulate these processes.