title: Oxidative stress contributes to autophagy induction in response to endoplasmic reticulum stress in Chlamydomonas reinhardtii.
abstract: The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) results in the activation of stress responses, such as the unfolded protein response or the catabolic process of autophagy to ultimately recover cellular homeostasis. ER stress also promotes the production of reactive oxygen species, which play an important role in autophagy regulation. However, it remains unknown whether reactive oxygen species are involved in ER stress-induced autophagy. In this study, we provide evidence connecting redox imbalance caused by ER stress and autophagy activation in the model unicellular green alga Chlamydomonas reinhardtii. Treatment of C. reinhardtii cells with the ER stressors tunicamycin or dithiothreitol resulted in up-regulation of the expression of genes encoding ER resident endoplasmic reticulum oxidoreductin1 oxidoreductase and protein disulfide isomerases. ER stress also triggered autophagy in C. reinhardtii based on the protein abundance, lipidation, cellular distribution, and mRNA levels of the autophagy marker ATG8. Moreover, increases in the oxidation of the glutathione pool and the expression of oxidative stress-related genes were detected in tunicamycin-treated cells. Our results revealed that the antioxidant glutathione partially suppressed ER stress-induced autophagy and decreased the toxicity of tunicamycin, suggesting that oxidative stress participates in the control of autophagy in response to ER stress in C. reinhardtii In close agreement, we also found that autophagy activation by tunicamycin was more pronounced in the C. reinhardtii sor1 mutant, which shows increased expression of oxidative stress-related genes.
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, 41092 Seville, Spain (M.P.-M., J.L.C.); andCentre National de la Recherche Scientifique (M.E.P.-P.; S.D.L.) andSorbonne Universités, Université Pierre et Marie Curie, University of Paris 06 (M.E.P.-P.; S.D.L.), Unité Mixte de Recherche 8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France.
authors.forename: Marta
authors.initials: M
authors.lastname: Pérez-Martín
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, 41092 Seville, Spain (M.P.-M., J.L.C.); andCentre National de la Recherche Scientifique (M.E.P.-P.; S.D.L.) andSorbonne Universités, Université Pierre et Marie Curie, University of Paris 06 (M.E.P.-P.; S.D.L.), Unité Mixte de Recherche 8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France.
authors.forename: María Esther
authors.initials: ME
authors.lastname: Pérez-Pérez
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, 41092 Seville, Spain (M.P.-M., J.L.C.); andCentre National de la Recherche Scientifique (M.E.P.-P.; S.D.L.) andSorbonne Universités, Université Pierre et Marie Curie, University of Paris 06 (M.E.P.-P.; S.D.L.), Unité Mixte de Recherche 8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France.
authors.forename: Stéphane D
authors.initials: SD
authors.lastname: Lemaire
authors.affiliation: Instituto de Bioquímica Vegetal y Fotosíntesis, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, 41092 Seville, Spain (M.P.-M., J.L.C.); andCentre National de la Recherche Scientifique (M.E.P.-P.; S.D.L.) andSorbonne Universités, Université Pierre et Marie Curie, University of Paris 06 (M.E.P.-P.; S.D.L.), Unité Mixte de Recherche 8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France crespo@ibvf.csic.es.
authors.forename: José L
authors.initials: JL
authors.lastname: Crespo
mesh_terms: D001343:Autophagy; D016825:Chlamydomonas reinhardtii / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D014415:Tunicamycin; D005978:Glutathione; D004229:Dithiothreitol