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Bulthuis, E.P.* ; Einer, C. ; Distelmaier, F.* ; Groh, L.* ; van Emst-de Vries, S.E.* ; van de Westerlo, E.* ; van de Wal, M.* ; Wagenaars, J.* ; Rodenburg, R.J.* ; Smeitink, J.A.M.* ; Riksen, N.P.* ; Willems, P.H.G.M.* ; Adjobo-Hermans, M.J.W.* ; Zischka, H. ; Koopman, W.J.H.*

The decylTPP mitochondria-targeting moiety lowers electron transport chain supercomplex levels in primary human skin fibroblasts.

Free Radical Biol. Med. 188, 434-446 (2022)
Verlagsversion Forschungsdaten DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Attachment of cargo molecules to lipophilic triphenylphosphonium (TPP+) cations is a widely applied strategy for mitochondrial targeting. We previously demonstrated that the vitamin E-derived antioxidant Trolox increases the levels of active mitochondrial complex I (CI), the first complex of the electron transport chain (ETC), in primary human skin fibroblasts (PHSFs) of Leigh Syndrome (LS) patients with isolated CI deficiency. Primed by this finding, we here studied the cellular effects of mitochondria-targeted Trolox (MitoE10), mitochondria-targeted ubiquinone (MitoQ10) and their mitochondria-targeting moiety decylTPP (C10-TPP+). Chronic treatment (96 h) with these molecules of PHSFs from a healthy subject and an LS patient with isolated CI deficiency (NDUFS7-V122 M mutation) did not greatly affect cell number. Unexpectedly, this treatment reduced CI levels/activity, lowered the amount of ETC supercomplexes, inhibited mitochondrial oxygen consumption, increased extracellular acidification, altered mitochondrial morphology and stimulated hydroethidine oxidation. We conclude that the mitochondria-targeting decylTPP moiety is responsible for the observed effects and advocate that every study employing alkylTPP-mediated mitochondrial targeting should routinely include control experiments with the corresponding alkylTPP moiety.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Complex I ; Glycolysis ; Mitochondrial Targeting ; Supercomplexes ; Trolox ; Decyltpp
ISSN (print) / ISBN 0891-5849
e-ISSN 1873-4596
Quellenangaben Band: 188, Heft: , Seiten: 434-446 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Förderungen Nederlandse Organisatie voor Wetenschappelijk onderzoek
ZON-MW
TIM foundation
PM-Rare
Netherlands Organization for Health Research and Development-Medical Sciences
Energy4All foundation