Laleve A. auteur aut IRD Panozzo C. auteur aut IRD Kuhl I. auteur aut IRD Bourand-Plantefol A. auteur aut IRD Ostojic J. auteur aut IRD Sissoko A. auteur aut IRD Tribouillard-Tanvier D. auteur aut IRD Cornu D. auteur aut IRD Burg A. auteur aut IRD Meunier B. auteur aut IRD Blondel M. auteur aut IRD Clain J. auteur aut IRD Bonnefoy N. auteur aut IRD Duval Romain auteur aut IRD Dujardin G. auteur aut IRD text journalArticle eng text/pdf born digital access Artemisinin and its derivatives kill malaria parasites and inhibit the proliferation of cancer cells. In both processes, heme was shown to play a key role in artemisinin bioactivation. We found that artemisinin and clinical artemisinin derivatives are able to compensate for a mutation in the yeast Bcsl protein, a key chaperon involved in biogenesis of the mitochondrial respiratory complex III. The equivalent Bcsl variant causes an encephalopathy in human by affecting complex III assembly. We show that artemisinin derivatives decrease the content of mitochondrial cytochromes and disturb the maturation of the complex III cytochrome cl. This last effect is likely responsible for the compensation by decreasing the detrimental over-accumulation of the inactive pre-complex III observed in the bcs1 mutant. We further show that a fluorescent dihydroartemisinin probe rapidly accumulates in the mitochondrial network and targets cytochromes c and c1 in yeast, human cells and isolated mitochondria. in vitro this probe interacts with purified cytochrome c only under reducing conditions and we detect cytochrome c-dihydroartemisinin covalent adducts by mass spectrometry analyses. We propose that reduced mitochondrial c-type cytochromes act as both targets and mediators of artemisinin bioactivation in yeast and human cells. specialized Mitochondria c-Type cytochromes Artemisinins Fluorescent probe Bcs1 076 020 050 1867 5 art. 118661 [11 ] 2020 0167-4889 https://www.documentation.ird.fr/hor/fdi:010078876 10.1016/j.bbamcr.2020.118661 0167-4889 [F B010078876] https://www.documentation.ird.fr/hor/fdi:010078876 https://www.documentation.ird.fr/intranet/publi/2020/04/010078876.pdf Accès réservé (Intranet de l'IRD) IRD - Base Horizon / Pleins textes 2020-05-19 2025-02-24 fdi:010078876 fre