title: Changes in Drosophila mitochondrial proteins following chaperone-mediated lifespan extension confirm a role of Hsp22 in mitochondrial UPR and reveal a mitochondrial localization for cathepsin D.
abstract: Hsp22 is a small mitochondrial heat shock protein (sHSP) preferentially up-regulated during aging in Drosophila melanogaster. Its developmental expression is strictly regulated and it is rapidly induced in conditions of stress. Hsp22 is one of the few sHSP to be localized inside mitochondria, and is the first sHSP to be involved in the mitochondrial unfolding protein response (UPR(MT)) together with Hsp60, mitochondrial Hsp70 and TRAP1. The UPR(MT) is a pro-longevity mechanism, and interestingly Hsp22 over-expression by-itself increases lifespan and resistance to stress. To unveil the effect of Hsp22 on the mitochondrial proteome, comparative IEF/SDS polyacrylamide 2D gels were done on mitochondria from Hsp22+ flies and controls. Among the proteins influenced by Hsp22 expression were proteins from the electron transport chain (ETC), the TCA cycle and mitochondrial Hsp70. Hsp22 co-migrates with ETC components and its over-expression is associated with an increase in mitochondrial protease activity. Interestingly, the only protease that showed significant changes upon Hsp22 over-expression in the comparative IEF/SDS-PAGE analysis was cathepsin D, which is localized in mitochondria in addition to lysosome in D. melanogaster as evidenced by cellular fractionation. Together the results are consistent with a role of Hsp22 in the UPR(MT) and in mitochondrial proteostasis.
authors.affiliation: Laboratoire de Génétique Cellulaire et Développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Morrow
authors.affiliation: Laboratoire de Génétique Cellulaire et Développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Laboratoire de Génétique Cellulaire et Développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Ornella
authors.initials: O
authors.lastname: Pellerito
authors.affiliation: Laboratoire de Génétique Cellulaire et Développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Bourrelle-Langlois
authors.affiliation: Laboratoire de Génétique Cellulaire et Développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Le Pécheur
authors.affiliation: ProteoSys AG, Mainz, Germany.
authors.forename: Karlfried
authors.initials: K
authors.lastname: Groebe
authors.affiliation: Laboratoire de Génétique Cellulaire et Développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Institut de Biologie Intégrative et des Systèmes (IBIS) and PROTEO, Université Laval, Québec, G1V 0A6, Canada. Electronic address: robert.tanguay@ibis.ulaval.ca.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tanguay
mesh_terms: D000818:Animals; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; C490752:Hsp22 protein, Drosophila; D024101:Mitochondrial Proteins; D002402:Cathepsin D
keywords: Cathepsin D; Drosophila melanogaster Hsp22; Mitochondria; Mitochondrial unfolding protein response; Small heat shock protein