Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Charles P. Najt; Santosh Adhikari; Timothy D. Heden; Wenqi Cui; Erica R. Gansemer; Adam J. Rauckhorst; Todd W. Markowski; LeeAnn Higgins; Evan W. Kerr; Matthew D. Boyum; Jonas Alvarez; Sophia Brunko; Dushyant Mehra; Elias M. Puchner; Eric B. Taylor; Douglas G. Mashek

doi:10.1016/j.celrep.2023.112435

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Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Journal article

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Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism

Charles P. Najt, Santosh Adhikari, Timothy D. Heden, Wenqi Cui, Erica R. Gansemer, Adam J. Rauckhorst, Todd W. Markowski, LeeAnn Higgins, Evan W. Kerr, Matthew D. Boyum, …

Cell reports (Cambridge), Vol.42(5), pp.112435-112435

05/30/2023

DOI: 10.1016/j.celrep.2023.112435

PMCID: PMC10278152

PMID: 37104088

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Abstract

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 mitochondria (PDM) and cytosolic mitochondria (CM) reveals 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 confirms 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 medium. Additionally, mitochondrion-associated membranes (MAM) around PDM and CM differ 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. [Display omitted] •CM are enriched in oxidative proteins and utilize FAs during fasting•PDM are enriched in lipid anabolism proteins and facilitate FA esterification•MAM around PDM and CM are unique and differentially regulate lipid metabolism•PLIN5 regulates the proteomes and functions of mitochondrial and MAM subpopulations Najt et al. reveal that the proteomes and functions of subpopulations of hepatic mitochondria and MAM differ based on their interactions with LDs. FAs are selectively trafficked to and oxidized in CM, especially during fasting, whereas PDM and associated MAM facilitate FA esterification and LD expansion.

cytosolic mitochondria

fatty acids

lipid anabolism

lipid catabolism

lipid droplets

MAM

organelle interactions

peridroplet mitochondria

perilipin 5

single-molecule localization microscopy

Details

Title: Subtitle: Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism
Creators: Charles P. Najt - University of Minnesota
Santosh Adhikari - University of Minnesota
Timothy D. Heden - University of Minnesota
Wenqi Cui - University of Minnesota
Erica R. Gansemer - University of Minnesota
Adam J. Rauckhorst - University of Iowa
Todd W. Markowski - University of Minnesota
LeeAnn Higgins - University of Minnesota
Evan W. Kerr - University of Minnesota
Matthew D. Boyum - University of Minnesota
Jonas Alvarez - University of Minnesota
Sophia Brunko - University of Minnesota
Dushyant Mehra - University of Minnesota
Elias M. Puchner - University of Minnesota
Eric B. Taylor - University of Iowa
Douglas G. Mashek - University of Minnesota
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.42(5), pp.112435-112435
DOI: 10.1016/j.celrep.2023.112435
PMID: 37104088
PMCID: PMC10278152
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: Elsevier Inc
Language: English
Date published: 05/30/2023
Academic Unit: Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984446449402771

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