title: Effects of a Sublethal and Transient Stress of the Endoplasmic Reticulum on the Mitochondrial Population.
abstract: Endoplasmic reticulum (ER) and mitochondria are not discrete intracellular organelles but establish close physical and functional interactions involved in several biological processes including mitochondrial bioenergetics, calcium homeostasis, lipid synthesis, and the regulation of apoptotic cell death pathways. As many cell types might face a transient and sublethal ER stress during their lifetime, it is thus likely that the adaptive UPR response might affect the mitochondrial population. The aim of this work was to study the putative effects of a non-lethal and transient endoplasmic reticulum stress on the mitochondrial population in HepG2 cells. The results show that thapsigargin and brefeldin A, used to induce a transient and sublethal ER stress, rapidly lead to the fragmentation of the mitochondrial network associated with a decrease in mitochondrial membrane potential, O2 (•-) production and less efficient respiration. These changes in mitochondrial function are transient and preceded by the phosphorylation of JNK. Inhibition of JNK activation by SP600125 prevents the decrease in O2 (•-) production and the mitochondrial network fragmentation observed in cells exposed to the ER stress but has no impact on the reduction of the mitochondrial membrane potential. In conclusion, our data show that a non-lethal and transient ER stress triggers a rapid activation of JNK without inducing apoptosis, leading to the fragmentation of the mitochondrial network and a reduction of O2 (•-) production. J. Cell. Physiol. 231: 1913-1931, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Kayleen
authors.initials: K
authors.lastname: Vannuvel
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Van Steenbrugge
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Demazy
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Ninane
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Antoine
authors.initials: A
authors.lastname: Fattaccioli
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Maude
authors.initials: M
authors.lastname: Fransolet
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Renard
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
authors.affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Arnould
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology*
chemical_list: D019284:Thapsigargin