Age-dependent posttranslational modifications of voltage-dependent anion channel 1.
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.
Groebe
Karlfried
K
ProteoSys AG, Carl Zeiss Strasse 51, Mainz, Germany.
Klemm-Manns
Martina
M
Schwall
Gerhard P
GP
Hübenthal
Heiko
H
Unterluggauer
Herrmann
H
Jansen-Dürr
Pidder
P
Tanguay
Robert M
RM
Morrow
Geneviève
G
Schrattenholz
André
A
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*
D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; C490752:Hsp22 protein, Drosophila; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1