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Brunner, S.* ; Höring, M.* ; Liebisch, G.* ; Schweizer, S.* ; Scheiber, J.* ; Giansanti, P.* ; Hidrobo, M.S.* ; Hermeling, S.* ; Oeckl, J.* ; Prudente de Mello, N. ; Perocchi, F. ; Seeliger, C.* ; Strohmeyer, A.* ; Klingenspor, M.* ; Plagge, J.* ; Küster, B.* ; Burkhardt, R.* ; Janssen, K.P.* ; Ecker, J.*

Mitochondrial lipidomes are tissue specific - low cholesterol contents relate to UCP1 activity.

Life Sci. All. 7:e202402828 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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, STARD3 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Brown Adipose-tissue; Tandem Mass-spectrometry; Fatty-acid Synthesis; Physiological Regulation; Uncoupling Protein; Flip-flop; Transport; Phospholipids; Mechanism; Cells
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Zeitschrift Life Science Alliance
Quellenangaben Band: 7, Heft: 8, Seiten: , Artikelnummer: e202402828 Supplement: ,
Verlag EMBO Press
Verlagsort Heidelberg
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen Deutsche Forschungsgemeinschaft (DFG)