Mitochondrial Ca²⁺ uptake depends on the spatial and temporal profile of cytosolic Ca²⁺ signals

Collins, Tony J.; Lipp, Peter; Berridge, Michael J. and Bootman, Martin D. (2001). Mitochondrial Ca²⁺ uptake depends on the spatial and temporal profile of cytosolic Ca²⁺ signals. Journal of Biological Chemistry, 276(28) pp. 26411–26420.

DOI: https://doi.org/10.1074/jbc.M101101200

URL: http://www.jbc.org/content/276/28/26411.full.pdf+h...

Abstract

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⁺ (Ca²⁺_mit) uptake was stimulated by inositol 1,4,5-trisphosphate (InsP₃)-evoked Ca²⁺ release, capacitative Ca²⁺ entry, and Ca²⁺ leaking from the endoplasmic reticulum. For each Ca²⁺ source, the relationship between cytosolic Ca²⁺ (Ca²⁺_cyt) concentration and Ca²⁺_mit was complex. With Ca²⁺_cyt < 300 nM, a slow and persistent Ca²⁺_mit uptake was observed. If Ca²⁺_cyt increased above ~ 400 nM, Ca²⁺_mit uptake accelerated sharply. For equivalent Ca²⁺_cyt increases, the rate of Ca²⁺_mit rise was greater with InsP₃-evoked Ca²⁺ signals than any other source. Spatial variation of the Ca²⁺_mit response was observed within individual cells. Both the fraction of responsive mitochondria and the amplitude of the Ca²⁺_mit response were graded in direct proportion to stimulus concentration. Trains of repetitive Ca²⁺ oscillations did not maintain elevated Ca²⁺_mit levels. Only low frequency Ca²⁺ transients (<1/15 min) evoked repetitive Ca²⁺_mit signals. Our data indicate that there is a lag between Ca²⁺_cyt and Ca²⁺_mit increases but that mitochondria will accumulate calcium when it is elevated over basal levels regardless of its source. Furthermore, in addition to the characteristics of Ca²⁺ signals, Ca²⁺ uniporter desensitization and proximity of mitochondria to InsP₃ receptors modulate mitochondrial Ca²⁺ responses.

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