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.
LanguageEnglish
Pages1913
Number of pages1931
JournalJournal of Cellular Physiology
DOIs
Publication statusPublished - 1 Sep 2016

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Endoplasmic Reticulum Stress
Population
Mitochondrial Membrane Potential
Chemical activation
Membranes
Brefeldin A
Biological Phenomena
Phosphorylation
Mitochondria
Thapsigargin
Hep G2 Cells
Cell death
Endoplasmic Reticulum
Organelles
Energy Metabolism
Respiration
Homeostasis
Cell Death
Apoptosis
Calcium

Cite this

@article{1834fd529693494fb74cae26d6513ac0,
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 fragmentationof 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 thedecrease 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 areduction of O2.- production.",
author = "Kayleen Vannuvel and {Van Steenbrugge}, Martine and Catherine Demazy and No{\"e}lle Ninane and Antoine Fattaccioli and Maude Fransolet and Patricia Renard and Martine Raes and Thierry Arnould",
note = "This article is protected by copyright. All rights reserved.",
year = "2016",
month = "9",
day = "1",
doi = "10.1002/jcp.25292",
language = "English",
pages = "1913",
journal = "Journal of Cellular Physiology",
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T1 - Effects of a sublethal and transient stress of the endoplasmic reticulum on the mitochondrial population

AU - Vannuvel, Kayleen

AU - Van Steenbrugge, Martine

AU - Demazy, Catherine

AU - Ninane, Noëlle

AU - Fattaccioli, Antoine

AU - Fransolet, Maude

AU - Renard, Patricia

AU - Raes, Martine

AU - Arnould, Thierry

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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 fragmentationof 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 thedecrease 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 areduction of O2.- production.

AB - 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 fragmentationof 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 thedecrease 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 areduction of O2.- production.

U2 - 10.1002/jcp.25292

DO - 10.1002/jcp.25292

M3 - Article

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JO - Journal of Cellular Physiology

T2 - Journal of Cellular Physiology

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