RT info:eu-repo/semantics/article
T1 Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects.
A1 Hernández Fernaud, Juan Ramón
A1 Tyrakis, Petros A.
A1 Yurkovich, Marie E.
A1 Sciacovelli, Marco
A1 Papachristou, Evangelia K.
A1 Bridges, Hannah R.
A1 Gaude, Edoardo
A1 Schreiner, Alexander
A1 D’Santos, Clive
A1 Hirst, Judy
A1 Springett, Roger
A1 Griffiths, John R.
A1 Frezza, Christian
A2 BioquímicaMicrobiología, Biología Celular y Genética
A2 School of Life Sciences. University of Warwick.
AB Fumarate hydratase (FH) is an enzyme of the tricarboxylicacid (TCA) cycle mutated in hereditary andsporadic cancers. Despite recent advances in understandingits role in tumorigenesis, the effects of FHloss on mitochondrial metabolism are still unclear.Here, we used mouse and human cell lines to assessmitochondrial function of FH-deficient cells. Wefound that human and mouse FH-deficient cellsexhibit decreased respiration, accompanied by avarying degree of dysfunction of respiratory chain(RC) complex I and II. Moreover, we show that fumarateinduces succination of key components of theiron-sulfur cluster biogenesis family of proteins,leading to defects in the biogenesis of iron-sulfurclusters that affect complex I function. We alsodemonstrate that suppression of complex II activityis caused by product inhibition due to fumarate accumulation.Overall, our work provides evidence thatthe loss of a single TCA cycle enzyme is sufficientto cause combined RC activity dysfunction.
YR 2017
FD 2017
LK http://riull.ull.es/xmlui/handle/915/38868
UL http://riull.ull.es/xmlui/handle/915/38868
LA en
NO DOI: 10.1016/j.celrep.2017.09.092
DS Repositorio institucional de la Universidad de La Laguna
RD 16-may-2025