Tj. Collins et al., Mitochondrial Ca2+ uptake depends on the spatial and temporal profile of cytosolic Ca2+ signals, J BIOL CHEM, 276(28), 2001, pp. 26411-26420
Using confocal imaging of Rhod-2-loaded HeLa cells, we examined the ability
of mitochondria to sequester Ca2+ signals arising from different sources.
Mitochondrial Ca2+ (Ca-mit(2+)) uptake was stimulated by inositol 1,4,5-tri
sphosphate (InsP(3))-evoked Ca2+ release, capacitative Ca2+ entry, and Ca2 leaking from the endoplasmic reticulum, For each Ca2+ source, the relation
ship between cytosolic Ca2+ (Ca-cyt(2+)) concentration and Ca-mit(2+) was c
omplex. With Ca-cyt(2+) < 300 nM, a slow and persistent Ca-mit(2+) uptake w
as observed. If Ca-cyt(2+) increased above similar to 400 nM, Ca-mit(2+) up
take accelerated sharply. For equivalent Ca-mit(2+) increases, the rate of
Ca-mit(2+) rise was greater with InsP(3)-evoked Ca2+ signals than any other
source. Spatial variation of the Ca-mit(2+) response was observed within i
ndividual cells. Both the fraction of responsive mitochondria and the ampli
tude of the Ca-mit(2+) response were graded in direct proportion to stimulu
s concentration. Trains of repetitive Ca2+ oscillations did not maintain el
evated Ca-mit(2+) levels. Only low frequency Ca2+ transients (<1/15 min) ev
oked repetitive Ca-mit(2+) signals. Our data indicate that there is a lag b
etween Ca-cyt(2+) and Ca-mit(2+) increases but that mitochondria will accum
ulate calcium when it is elevated over basal levels regardless of its sourc
e. Furthermore, in addition to the characteristics of Ca2+ signals, Ca2+ un
iporter desensitization and proximity of mitochondria to InsP(3) receptors
modulate mitochondrial Ca2+ responses.