Supression of StarD7 promotes Endoplasmic Reticulum Stress and induces ROS production

FLORES MARTIN J; PANZETTA DUTARI G; REYNA L; GENTI RAIMONDI S; RIDANO, M.E

Córdoba

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

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

StarD7 transcript encodes an intracellular lipid transport protein, 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 decreased ABCG2 multidrug transporter level, cell migration, proliferation, and phospholipid synthesis. Since lipids and proteins transport between organelles is an important process in the organization of the different cell compartments, we hypothesized that StarD7 may be involved in maintaining cell homeostasis. We analyzed the effect of StarD7 silencing on 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 (UPR) pathway associated with an increased basal ROS and augmented levels of the heme oxygenase-1 and catalase enzymes. Also, StarD7 silencing reduced cell viability after H2O2 exposure. Moreover, downregulation of the tumor suppressor p53 by a degradation mechanism was established in StarD7 siRNA cells. Finally, no changes in autophagy and apoptosis were observed in StarD7 siRNA treated cells respect to control. Together these results indicate that StarD7 beyond its role in lipid transport contributes to maintain cellular redox homeostasis.