Description
Organelle interactions play a significant role in compartmentalizing metabolism and signaling. Lipid droplets (LDs) interact with numerous organelles including mitochondria, which is largely assumed to facilitate lipid transfer and catabolism. However, quantitative proteomics of hepatic peridroplet (PDM) and cytosolic mitochondria (CM) revealed that CM are enriched in proteins comprising various oxidative metabolism pathways whereas PDM are enriched in proteins involved in lipid anabolism. Isotope tracing and super-resolution imaging confirmed that fatty acids (FAs) are selectively trafficked to and oxidized in CM during fasting. In contrast, PDM facilitate FA esterification and LD expansion in nutrient-replete media. Additionally, mitochondrial-associated membranes (MAMs) around PDM and CM differed in their proteomes and ability to support distinct lipid metabolic pathways. We conclude that CM and CM-MAM support lipid catabolic pathways whereas PDM and PDM-MAM allow hepatocytes to efficiently store excess lipids in LDs to prevent lipotoxicity in contrast to existing dogma.
[doi:10.25345/C5S17T32W]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Cytosolic mitochondria, fatty acids, lipid anabolism, lipid catabolism, lipid droplets, MAM, organelle interactions, peridroplet mitochondria, perilipin 5
Contact
Principal Investigators:
(in alphabetical order)
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Douglas Mashek, University of Minnesota, United States
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cpnajt
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