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Ndoci, M. ; Bhattacharya, S. ; Agrawal, I.* ; Hinze, Y.* ; Lemke, K.* ; Schumacher, A.L.* ; Uijttewaal, E.* ; Elling, U.* ; Lawo, S.* ; Giavalisco, P.* ; Langer, T.* ; Deshwal, S.

Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress.

J. Cell Biol. 225:e202507174 (2026)
Verlagsversion Forschungsdaten DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
Coenzyme Q (CoQ) is a hydrophobic lipid primarily synthesized in the mitochondria, though it is also present in non-mitochondrial membranes. However, the metabolic pathways that regulate intracellular CoQ distribution are unknown. This study identifies a key role for the mevalonate pathway in regulating CoQ distribution. The mevalonate pathway synthesizes isopentenyl pyrophosphate (IPP) as the precursor metabolite for both CoQ and cholesterol. We show that CoQ synthesis remains stable regardless of whether the mevalonate pathway is upregulated or downregulated. Upregulation of HMG-CoA reductase (HMGCR), indicative of increased mevalonate flux, enhances cholesterol ester synthesis without altering CoQ levels. When the pathway is downregulated, cholesterol synthesis declines, yet mitochondrial CoQ levels are preserved. Under these limiting conditions, mitochondria reduce CoQ export to maintain their internal CoQ pool. While this adaptation sustains mitochondrial respiration, it diminishes extramitochondrial CoQ availability and sensitizes cells to ferroptosis. These findings uncover a mitochondria-driven mechanism that preserves respiratory function by prioritizing CoQ retention during metabolic stress.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0021-9525
e-ISSN 1540-8140
Zeitschrift Journal of Cell Biology, The
Quellenangaben Band: 225, Heft: 8, Seiten: , Artikelnummer: e202507174 Supplement: ,
Verlag Rockefeller University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)