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Posted: Fri Oct 03, 2008 9:03 pm Post subject: Mitochondrial reactive oxygen species and Ca2+ signaling. |
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Am J Physiol Cell Physiol. 2006 Nov;291(5):C1082-8. Epub 2006 Jun 7.
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Mitochondrial reactive oxygen species and Ca2+ signaling.Camello-
Almaraz C, Gomez-Pinilla PJ, Pozo MJ, Camello PJ.
Dept. of Physiology, University of Extremadura, 10071 Cáceres, Spain.
Mitochondria are an important source of reactive oxygen species (ROS)
formed as a side product of oxidative phosphorylation. The main sites
of oxidant production are complex I and complex III, where electrons
flowing from reduced substrates are occasionally transferred to oxygen
to form superoxide anion and derived products. These highly reactive
compounds have a well-known role in pathological states and in some
cellular responses. However, although their link with Ca(2+) is well
studied in cell death, it has been hardly investigated in normal
cytosolic calcium concentration ([Ca(2+)](i)) signals. Several Ca(2+)
transport systems are modulated by oxidation. Oxidation increases the
activity of inositol 1,4,5-trisphosphate and ryanodine receptors, the
main channels releasing Ca(2+) from intracellular stores in response
to cellular stimulation. On the other hand, mitochondria are known to
control [Ca(2+)](i) signals by Ca(2+) uptake and release during
cytosolic calcium mobilization, specially in mitochondria situated
close to Ca(2+) release channels. Mitochondrial inhibitors modify
calcium signals in numerous cell types, including oscillations evoked
by physiological stimulus. Although these inhibitors reduce
mitochondrial Ca(2+) uptake, they also impair ROS production in
several systems. In keeping with this effect, recent reports show that
antioxidants or oxidant scavengers also inhibit physiological calcium
signals. Furthermore, there is evidence that mitochondria generate ROS
in response to cell stimulation, an effect suppressed by mitochondrial
inhibitors that simultaneously block [Ca(2+)](i) signals. Together,
the data reviewed here indicate that Ca(2+)-mobilizing stimulus
generates mitochondrial ROS, which, in turn, facilitate [Ca(2+)](i)
signals, a new aspect in the biology of mitochondria. Finally, the
potential implications for biological modeling are discussed.
PMID: 16760264 [PubMed - indexed for MEDLINE] |
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