title: Age-dependent posttranslational modifications of voltage-dependent anion channel 1.
abstract: The accumulation of oxidative damage in mitochondrial proteins, membranes and DNA during ageing is supposed to lead to mitochondrial inactivation, downstream molecular impairments and subsequent decline of biological systems. In a quantitative study investigating the age-related changes of mitochondrial proteins on the level of oxidative posttranslational modifications, we previously found a set of conserved biomarkers across ageing models in five species with consistent oxidative break-up of tryptophan residues and formation of N-formyl kynurenine. In an additional proteomic profiling of a long-living Drosophila mutant overexpressing mitochondrial Hsp22 and controls, we found age-related redundant isoforms of voltage-dependent anion channel 1 (VDAC-1). A re-examination of data from human umbilical vein endothelial cells (with normal and chemically accelerated in vitro ageing), revealed similar age-dependent alterations of voltage-dependent anion channel isoforms. Building on these results, we examined the expression of VDAC-1 in an in vitro model of excitotoxicity. We show that glutamate-induced calcium toxicity in neurons induces changes of voltage-dependent anion channel 1 related to downstream events of mitochondrial apoptosis like poly-ADP-ribosylation.
authors.affiliation: ProteoSys AG, Carl Zeiss Strasse 51, Mainz, Germany.
authors.forename: Karlfried
authors.initials: K
authors.lastname: Groebe
authors.forename: Martina
authors.initials: M
authors.lastname: Klemm-Manns
authors.forename: Gerhard P
authors.initials: GP
authors.lastname: Schwall
authors.forename: Heiko
authors.initials: H
authors.lastname: Hübenthal
authors.forename: Herrmann
authors.initials: H
authors.lastname: Unterluggauer
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tanguay
authors.forename: Geneviève
authors.initials: G
authors.lastname: Morrow
authors.forename: André
authors.initials: A
authors.lastname: Schrattenholz
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; C490752:Hsp22 protein, Drosophila; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1