Effects of a sublethal and transient stress of the endoplasmic reticulum on the mitochondrial population

Kayleen Vannuvel, Martine Van Steenbrugge, Catherine Demazy, Noëlle Ninane, Antoine Fattaccioli, Maude Fransolet, Patricia Renard, Martine Raes, Thierry Arnould

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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 preceeded 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 shows 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.
Original languageEnglish
Pages (from-to)1913
Number of pages1931
JournalJournal of Cellular Physiology
DOIs
Publication statusPublished - 1 Sep 2016

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    Organelle Crosstalk in Membrane Dynamics and Cell Signalling

    Thierry Arnould (Poster)

    26 Oct 201529 Oct 2015

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