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Mitochondrial peroxiredoxin‐5 as potential modulator of mitochondria‐ ER crosstalk in MPP + ‐induced cell death
Author(s) -
Simoni Stéphanie,
Linard Dominique,
Hermans Emmanuel,
Knoops Bernard,
Goemaere Julie
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12117
Subject(s) - mitochondrion , microbiology and biotechnology , peroxiredoxin , endoplasmic reticulum , calpain , inositol trisphosphate receptor , neurodegeneration , programmed cell death , intracellular , mitochondrial fission , biology , cytosol , chemistry , inositol , apoptosis , biochemistry , receptor , enzyme , pathology , medicine , peroxidase , disease
Peroxiredoxin‐5 ( PRDX 5) is an antioxidant enzyme which differs from the other peroxiredoxins with regards to its enzymatic mechanism, its high affinity for organic peroxides and peroxynitrite and its wide subcellular distribution. In particular, the mitochondrial isoform of PRDX 5 confers a remarkable cytoprotection toward oxidative stress to mammalian cells. Mitochondrial dysfunction and disruption of Ca 2+ homeostasis are implicated in neurodegeneration. Growing evidence supports that endoplasmic reticulum ( ER ) could operate in tandem with mitochondria to regulate intracellular Ca 2+ fluxes in neurodegenerative processes. Here, we overexpressed mitochondrial PRDX 5 in SH ‐ SY 5Y cells to dissect the role of this enzyme in 1‐methyl‐4‐phenylpyridinium ( MPP ) + ‐induced cell death. Our data show that mitochondria‐dependent apoptosis triggered by MPP + , assessed by the measurement of caspase‐9 activation and mitochondrial DNA damage, is prevented by mitochondrial PRDX 5 overexpression. Moreover, PRDX 5 overexpression blocks the increase in intracellular Ca 2+ , Ca 2+ ‐dependent activation of calpains and Bax cleavage. Finally, using Ca 2+ channel inhibitors (Nimodipine, Dantrolene and 2‐ APB ), we show that Ca 2+ release arises essentially from ER stores through 1,4,5‐inositol‐trisphosphate receptors ( IP 3 R). Altogether, our results suggest that the MPP + mitochondrial pathway of apoptosis is regulated by mitochondrial PRDX 5 in a process that could involve redox modulation of Ca 2+ transporters via a crosstalk between mitochondria and ER .