Suppression of StarD7 promotes endoplasmic stress and induces ROS production

FLORES-MARTÍN, JESICA; REYNA, LUCIANA; RIDANO, MAGALI EVELIN; PANZETTA-DUTARI, GRACIELA MARÍA; GENTI, SUSANA

Córdoba

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

StarD7 transcript encodes an intracellular lipid transport protein, a member of the START domain superfamily, which is involved in many physiological processes. It facilitates the delivery of phosphatidylcholine to the mitochondria and previous results indicated that StarD7 knockdown decreases ACBG2 multidrug transporter level, cell migration, proliferation, and phospholipid synthesis. Since lipids 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 generated alterations in mitochondria and ER morphology, initiating an unfolded protein response pathway associated with an increased basal ROS and augmented levels of the hemeoxygenase-1 and catalase enzymes. Also, StarD7 silencing reduced cell viability after H2O2 exposure. Moreover, downregulation of p53 by a degradation mechanism was established in StarD7 siRNA cells. Finally, no changes in 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.