title: Loss of Mitochondrial Function Impairs Lysosomes.
abstract: Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases.
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and Centre de recherche Biomed, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada and.
authors.forename: Julie
authors.initials: J
authors.lastname: Demers-Lamarche
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and Centre de recherche Biomed, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada and.
authors.forename: Gérald
authors.initials: G
authors.lastname: Guillebaud
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and.
authors.forename: Mouna
authors.initials: M
authors.lastname: Tlili
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and Centre de recherche Biomed, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada and.
authors.forename: Kiran
authors.initials: K
authors.lastname: Todkar
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and.
authors.forename: Noémie
authors.initials: N
authors.lastname: Bélanger
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and.
authors.forename: Martine
authors.initials: M
authors.lastname: Grondin
authors.affiliation: the Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
authors.forename: Angela P
authors.initials: AP
authors.lastname: Nguyen
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Michel
authors.affiliation: From the Groupe de Recherche en Signalisation Cellulaire, Département de Biologie Médicale and Centre de recherche Biomed, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada and marc.germain1@uqtr.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: Germain
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D051033:Apoptosis Inducing Factor; D045222:Electron Transport Chain Complex Proteins; D020558:GTP Phosphohydrolases; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D000099202:PTEN-Induced Putative Kinase; C494830:AIFM1 protein, mouse; C498809:Opa1 protein, mouse
keywords: Parkin; lysosome; mitochondria; neurodegenerative disease; reactive oxygen species (ROS)