About this Research Topic
Metabolic diseases are complex disorders caused by both genetics and acquired risk factors. Metabolic diseases differently impact multiple organs and tissues, such as liver, skeletal muscle, and adipose tissues. They are tightly interconnected to each other; for instance, obesity significantly increases the risk of type 2 diabetes mellitus (T2D), which potentially leads to cardiovascular disease and early mortality. To understand the underlying pathophysiologic and molecular mechanisms of metabolic diseases, further investigations are needed.
Mitochondria play crucial roles in cellular metabolism and signaling, and mitochondrial dysfunction has been observed in metabolic diseases. Recent research indicated that inter-organellar communication between mitochondria and other organelles may contribute to the pathology of metabolic diseases.
The study of the membrane contact sites (MCSs) is crucial in understanding the impact of communication between mitochondria and other organelles in the development of metabolic diseases. Indeed, MCSs are not only the sites for exchanging biochemical molecules, but also hot spots for signaling in metabolic pathways.
Specifically, the endoplasmic reticulum (ER) is the most described partner of mitochondria among mito-MCSs, as several tethering proteins have been identified. ER stress is proposed to develop insulin resistance in liver, skeletal muscle, and pancreas, as well as mitochondrial dysfunction. Recent studies showed alteration of mitochondria-ER contact sites in liver, skeletal muscle, pancreas of T2D patients and/or its animal model in mice. Further insights into how the malfunction of each organelle and the contact sites would affect each other, and eventually contribute to the development of the diseases, would reveal novel therapeutic targets.
An important consideration should be given to the lipid droplet (LD), which is a major fuel storage depot in cells. In healthy cells, lipid droplets contain neutral lipids. LD are attached to mitochondria via protein tethers, which provide a direct bridge to transfer neutral, fatty acids into the mitochondria for breakdown. During metabolic diseases, such as insulin resistance, fatty acids do not break down, resulting in intermediates of β-oxidation, causing cellular damage to nearby structures. This can be due to a decrease in the direct transfer of fatty acids from the lipid droplet into the mitochondria or due to an inhibition of the breakdown of the stored triglyceride into a single fatty acid. Despite these limitations in enzymatic breakdown of fatty acids, little remains known about how the direct transfer of fatty acids from LD to mitochondria changes with metabolic disease. Furthermore, additional research is needed to understand how temporary or permanent mito-LD interactions increase or decrease with metabolic disease. Despite these observations, how metabolic diseases impact mitochondria-to-organelle interaction, and vice versa, in various tissues remains unclear.
This Research Topic aims to investigate the implications of mitochondria-related organelle contact sites (mito-MCSs) in the context of metabolic diseases and how metabolic diseases impact mitochondria organellar interaction in various tissue.
We invite authors to submit manuscripts that elucidate the importance of mitochondria-organelle communication in metabolic diseases. We hope that this platform will provide an integrated perspective on how mitochondrial connections with themselves and with other organelles contribute to the etiology of the disease.
In this Research Topic, potential areas of interest may include, but are not limited to:
- mito-MCS (e.g. mitochondria-ER, -LD, -peroxisome) in metabolic diseases
- impacts of pharmacological interventions on mito-MCSs
The topic editors declare that they have no competing interests in relation to this topic.
Mitochondria play crucial roles in cellular metabolism and signaling, and mitochondrial dysfunction has been observed in metabolic diseases. Recent research indicated that inter-organellar communication between mitochondria and other organelles may contribute to the pathology of metabolic diseases.
The study of the membrane contact sites (MCSs) is crucial in understanding the impact of communication between mitochondria and other organelles in the development of metabolic diseases. Indeed, MCSs are not only the sites for exchanging biochemical molecules, but also hot spots for signaling in metabolic pathways.
Specifically, the endoplasmic reticulum (ER) is the most described partner of mitochondria among mito-MCSs, as several tethering proteins have been identified. ER stress is proposed to develop insulin resistance in liver, skeletal muscle, and pancreas, as well as mitochondrial dysfunction. Recent studies showed alteration of mitochondria-ER contact sites in liver, skeletal muscle, pancreas of T2D patients and/or its animal model in mice. Further insights into how the malfunction of each organelle and the contact sites would affect each other, and eventually contribute to the development of the diseases, would reveal novel therapeutic targets.
An important consideration should be given to the lipid droplet (LD), which is a major fuel storage depot in cells. In healthy cells, lipid droplets contain neutral lipids. LD are attached to mitochondria via protein tethers, which provide a direct bridge to transfer neutral, fatty acids into the mitochondria for breakdown. During metabolic diseases, such as insulin resistance, fatty acids do not break down, resulting in intermediates of β-oxidation, causing cellular damage to nearby structures. This can be due to a decrease in the direct transfer of fatty acids from the lipid droplet into the mitochondria or due to an inhibition of the breakdown of the stored triglyceride into a single fatty acid. Despite these limitations in enzymatic breakdown of fatty acids, little remains known about how the direct transfer of fatty acids from LD to mitochondria changes with metabolic disease. Furthermore, additional research is needed to understand how temporary or permanent mito-LD interactions increase or decrease with metabolic disease. Despite these observations, how metabolic diseases impact mitochondria-to-organelle interaction, and vice versa, in various tissues remains unclear.
This Research Topic aims to investigate the implications of mitochondria-related organelle contact sites (mito-MCSs) in the context of metabolic diseases and how metabolic diseases impact mitochondria organellar interaction in various tissue.
We invite authors to submit manuscripts that elucidate the importance of mitochondria-organelle communication in metabolic diseases. We hope that this platform will provide an integrated perspective on how mitochondrial connections with themselves and with other organelles contribute to the etiology of the disease.
In this Research Topic, potential areas of interest may include, but are not limited to:
- mito-MCS (e.g. mitochondria-ER, -LD, -peroxisome) in metabolic diseases
- impacts of pharmacological interventions on mito-MCSs
The topic editors declare that they have no competing interests in relation to this topic.
Keywords: Mitochondria, organelle interactions, metabolic diseases, membrane contact sites, endoplasmic reticulum, lipid droplet, peroxisome, type 2 diabetes, cardiovascular diseases
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