Abstract
Emerging evidence suggests that mitochondrion–endoplasmic reticulum (ER) and mitochondrion–lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion–ER and mitochondrion–LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion–LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are two major chronic liver diseases that cause serious health problems and are becoming huge economic burdens worldwide
Increasing evidence suggests that these organelles are not isolated but interconnected in order to facilitate the exchange of small molecules and metabolites through membrane contact sites (MCSs), which are crucial in maintaining organelle function and homeostasis, including lipid homeostasis [5,6,7]
As discussed above, free fatty acid (FFA) in the cytosol are toxic to the cells; we conceive that the formation of a direct channel to transport FFAs from lipid droplets (LDs) to mitochondria (FFAs oxidation/utilization) would be an efficient way to avoid high cytosolic concentrations of FFAs
Summary
Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are two major chronic liver diseases that cause serious health problems and are becoming huge economic burdens worldwide. VPS13D and TSG101 coordinately regulate the trafficking of the free fatty acid (FFA) between mitochondria and LDs at contact sites in cultured cells.
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