Mitochondrial Lipidomes Are Tissue Specific - Low Cholesterol Contents Relate to UCP1 Activity

Overview

Journal Life Sci Alliance

Specialties Biochemistry
Biology
Cell Biology
Molecular Biology

Date 2024 Jun 6

PMID 38843936

Authors

Sarah Brunner

Marcus Horing

Gerhard Liebisch

Sabine Schweizer

Josef Scheiber

Piero Giansanti

Maria Hidrobo

Sven Hermeling

Josef Oeckl

Natalia Prudente de Mello

Fabiana Perocchi

Claudine Seeliger

Akim Strohmeyer

Martin Klingenspor

Johannes Plagge

Bernhard Kuster

Ralph Burkhardt

Klaus-Peter Janssen

Josef Ecker

Affiliations

Soon will be listed here.

Abstract

Lipid composition is conserved within sub-cellular compartments to maintain cell function. Lipidomic analyses of liver, muscle, white and brown adipose tissue (BAT) mitochondria revealed substantial differences in their glycerophospholipid (GPL) and free cholesterol (FC) contents. The GPL to FC ratio was 50-fold higher in brown than white adipose tissue mitochondria. Their purity was verified by comparison of proteomes with ER and mitochondria-associated membranes. A lipid signature containing PC and FC, calculated from the lipidomic profiles, allowed differentiation of mitochondria from BAT of mice housed at different temperatures. Elevating FC in BAT mitochondria prevented uncoupling protein (UCP) 1 function, whereas increasing GPL boosted it. Similarly, overexpression facilitating mitochondrial FC import inhibited UCP1 function in primary brown adipocytes, whereas a knockdown promoted it. We conclude that the mitochondrial GPL/FC ratio is key for BAT function and propose that targeting it might be a promising strategy to promote UCP1 activity.

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