title: Mitochondrial P5, a member of protein disulphide isomerase family, suppresses oxidative stress-induced cell death.
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 H(2)O(2)- or rotenone-induced cell death is suppressed in MTS-P5 cells, which stably express P5 in mitochondria. H(2)O(2)-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 H(2)O(2) 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 H(2)O(2) exposure. These results suggest that mitochondrial P5 may upregulate tricarboxylic acid cycle and possibly, other intramitochondrial metabolism.
authors.affiliation: Faculty of Bioscience, Nagahama Institute of Bioscience and Technology, Nagahama, 526-0829, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shitara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tonohora
authors.forename: Takahiro
authors.initials: T
authors.lastname: Goto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Makino
authors.forename: Masanao
authors.initials: M
authors.lastname: Miwa
authors.forename: Tohru
authors.initials: T
authors.lastname: Komiya
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D018384:Oxidative Stress; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051033:Apoptosis Inducing Factor; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C526507:Pdia6 protein, mouse; D019704:Protein Disulfide-Isomerases