Age-dependent posttranslational modifications of voltage-dependent anion channel 1

作者：Groebe Karlfried; Klemm Manns Martina; Schwall Gerhard P; Huebenthal Heiko; Unterluggauer Herrmann; Jansen Duerr Pidder; Tanguay Robert M; Morrow Genevieve; Schrattenholz Andre^*

来源：Experimental Gerontology, 2010, 45(7-8): 632-637.

DOI：10.1016/j.exger.2010.02.006

• Mitochondrial permeability transition pore
• Voltage-dependent anion channel 1
• Quantitative proteomics
• Systems biology
• Oxidative posttranslational modifications
• Ageing model
• HSP 22
• Longevity
• Mitochondrial apoptosis
• PARP-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 over-expressing 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.

• 出版日期2010-8