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- Title
Mitochondrial P5, a member of protein disulphide isomerase family, suppresses oxidative stress-induced cell death.
- Authors
Shitara, Yu; Tonohora, Yuichi; Goto, Takahiro; Yamada, Yasuhiro; Miki, Takashi; Makino, Hirokazu; Miwa, Masanao; Komiya, Tohru
- Abstract
P5, one of the protein disulphide isomerase (PDI) family members, catalyses disulphide bond formation in proteins and exhibits molecular chaperone and calcium binding activities in vitro, whereas its physiological significance remains controversial. Recently, we have reported that P5 localizes not only in the ER but also in mitochondria, although it remains unclear so far about its physiological significance(s) of its dual localization. Here we report that H2O2− or rotenone-induced cell death is suppressed in MTS-P5 cells, which stably express P5 in mitochondria. H2O2-induced cell death in Saos-2 cells occurred, in large part, through caspase-independent and poly(ADP-ribose) polymerase (PARP)-dependent manner. In MTS-P5 cells challenged with H2O2 treatment, PARP was still activated, whereas release of cytochrome c or apoptosis-inducing factor and intramitochondrial superoxide generation were suppressed. We also found that mitochondrial P5 was in close contact with citrate synthase and maintained large parts of its activity under H2O2 exposure. These results suggest that mitochondrial P5 may upregulate tricarboxylic acid cycle and possibly, other intramitochondrial metabolism.
- Subjects
MITOCHONDRIA; PROTEIN disulfide isomerase; OXIDATIVE stress; CELL death; MOLECULAR chaperones; CALCIUM-binding proteins; KREBS cycle; METABOLISM
- Publication
Journal of Biochemistry, 2012, Vol 152, Issue 1, p73
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/jb/mvs034