Suppression of STARD7 promotes endoplasmic reticulum stress and induces Ros production

FLORES-MARTÍN J; REYNA, L.; RIDANO ME; PANZETTA DE DUTARI GM; GENTI-RAIMONDI SUSANA

Cordoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2016

LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

StarD7 transcript encodes an intracellular lipid transport protein, a member of the START domain superfamily, which is involved inmany physiological processes. It facilitates the delivery of phosphatidylcholine to the mitochondria and previous results indicated thatStarD7 knockdown decreases ACBG2 multidrug transporter level, cell migration, proliferation, and phospholipid synthesis. Sincelipids and protein transport between organelles are involved in the organization of the different cell compartments, we hypothesizedthat StarD7 may be involved in maintaining cell homeostasis. We analyzed the effect of StarD7 silencing on endoplasmic reticulum(ER) stress response and on the production of reactive oxygen species (ROS) in HepG2 cell line. StarD7 knockdown generatedalterations in mitochondria and ER morphology, initiating an unfolded protein response pathway associated with an increased basalROS and augmented levels of the hemeoxygenase-1 and catalase enzymes. Also, StarD7 silencing reduced cell viability after H2O2exposure. Moreover, downregulation of p53 by a degradation mechanism was established in StarD7 siRNA cells. Finally, no changesin autophagy and apoptosis were observed in StarD7 siRNA. Together these results indicate that, beyond its role in lipid transport,StarD7 contributes to maintain cellular redox homeostasis.