title: Mitochondrial reactive oxygen species and Ca2+ signaling.
abstract: 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.
authors.affiliation: Dept. of Physiology, University of Extremadura, 10071 Cáceres, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Camello-Almaraz
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Gomez-Pinilla
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pozo
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Camello
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D002118:Calcium