@article{fdi:010078876, title = {{A}rtemisinin and its derivatives target mitochondrial c-type cytochromes in yeast and human cells}, author = {{L}aleve, {A}. and {P}anozzo, {C}. and {K}uhl, {I}. and {B}ourand-{P}lantefol, {A}. and {O}stojic, {J}. and {S}issoko, {A}. and {T}ribouillard-{T}anvier, {D}. and {C}ornu, {D}. and {B}urg, {A}. and {M}eunier, {B}. and {B}londel, {M}. and {C}lain, {J}. and {B}onnefoy, {N}. and {D}uval, {R}omain and {D}ujardin, {G}.}, editor = {}, language = {{ENG}}, abstract = {{A}rtemisinin and its derivatives kill malaria parasites and inhibit the proliferation of cancer cells. {I}n both processes, heme was shown to play a key role in artemisinin bioactivation. {W}e found that artemisinin and clinical artemisinin derivatives are able to compensate for a mutation in the yeast {B}csl protein, a key chaperon involved in biogenesis of the mitochondrial respiratory complex {III}. {T}he equivalent {B}csl variant causes an encephalopathy in human by affecting complex {III} assembly. {W}e show that artemisinin derivatives decrease the content of mitochondrial cytochromes and disturb the maturation of the complex {III} cytochrome cl. {T}his 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. {W}e 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. {W}e propose that reduced mitochondrial c-type cytochromes act as both targets and mediators of artemisinin bioactivation in yeast and human cells.}, keywords = {{M}itochondria ; c-{T}ype cytochromes ; {A}rtemisinins ; {F}luorescent probe ; {B}cs1}, booktitle = {}, journal = {{B}iochimica et {B}iophysica {A}cta - {M}olecular {C}ell {R}esearch}, volume = {1867}, numero = {5}, pages = {art. 118661 [11 ]}, ISSN = {0167-4889}, year = {2020}, DOI = {10.1016/j.bbamcr.2020.118661}, URL = {https://www.documentation.ird.fr/hor/fdi:010078876}, }