title: SLP-2 negatively modulates mitochondrial sodium-calcium exchange.
abstract: Mitochondria play a major role in cellular calcium homeostasis. Despite decades of studies, the molecules that mediate and regulate the transport of calcium ions in and out of the mitochondrial matrix remain unknown. Here, we investigate whether SLP-2, an inner membrane mitochondrial protein of unknown function, modulates the activity of mitochondrial Ca(2+) transporters. In HeLa cells depleted of SLP-2, the amplitude and duration of mitochondrial Ca(2+) elevations evoked by agonists were decreased compared to control cells. SLP-2 depletion increased the rates of calcium extrusion from mitochondria. This effect disappeared upon Na(+) removal or addition of CGP-37157, an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger, and persisted in permeabilized cells exposed to a fixed cytosolic Na(+) and Ca(2+) concentration. The rates of mitochondrial Ca(2+) extrusion were prolonged in SLP-2 over-expressing cells, independently of the amplitude of mitochondrial Ca(2+) elevations. The amplitude of cytosolic Ca(2+) elevations was increased by SLP-2 depletion and decreased by SLP-2 over-expression. These data show that SLP-2 modulates mitochondrial calcium extrusion, thereby altering the ability of mitochondria to buffer Ca(2+) and to shape cytosolic Ca(2+) signals.
authors: Department of Cell Biology, University of Geneva, Switzerland.
authors: Sandrine
authors: S
authors: Da Cruz
authors: Umberto
authors: U
authors: De Marchi
authors: Maud
authors: M
authors: Frieden
authors: Philippe A
authors: PA
authors: Parone
authors: Jean-Claude
authors: JC
authors: Martinou
authors: Nicolas
authors: N
authors: Demaurex
mesh_terms: D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C406287:STOML2 protein, human; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; C079032:CGP 37157; D012964:Sodium; D002118:Calcium