RT info:eu-repo/semantics/article
T1 Modulation of Ca2+ release and Ca2+ oscillations in HeLa cells and fibroblasts by mitochondrial Ca2+ uniporter stimulation
A1 Vay, Laura
A1 Hernández San Miguel, Esther
A1 Santo Domingo, Jaime
A1 Domínguez Lobatón, María Carmen
A1 Moreno Díaz-Calderón, Alfredo
A1 Montero Zoccola, María Teresa
A1 Álvarez Martín, Javier
K1 Calcio en el organismo
AB The recent availability of activators of the mitochondrial Ca2+ uniporter allows directtesting of the influence of mitochondrial Ca2+ uptake on the overall Ca2+ homeostasisof the cell. We show here that activation of mitochondrial Ca2+ uptake by 4,4 ,4  -(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-inducedCa2+ release from the endoplasmic reticulum (ER) and that this effect is enhanced if themitochondrial Na+–Ca2+ exchanger is simultaneously inhibited with CGP37157. This suggeststhat both Ca2+ uptake and release from mitochondria control the ability of local Ca2+ microdomainsto produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP3Rs). Inaddition, the abilityof mitochondria tocontrolCa2+ release fromtheERallowsthemtomodulatecytosolic Ca2+ oscillations. In histamine stimulatedHeLa cells and human fibroblasts, both PPTand kaempferol initially stimulated and later inhibited oscillations, although kaempferol usuallyinduced a more prolonged period of stimulation. Both compounds were also able to induce thegeneration of Ca2+ oscillations in previously silent fibroblasts. Our data suggest that cytosolicCa2+ oscillations are exquisitely sensitive to the rates of mitochondrial Ca2+ uptake and release,which precisely control the size of the local Ca2+ microdomains around InsP3Rs and thus theability to produce feedback activation or inhibition of Ca2+ release.
PB Wiley
SN 0022-3751
YR 2007
FD 2007
LK http://uvadoc.uva.es/handle/10324/5984
UL http://uvadoc.uva.es/handle/10324/5984
LA eng
NO Journal of Physiology, 2007, vol. 580, n. 1, p. 39-49
NO Producción Científica
DS UVaDOC
RD 22-nov-2024