Mitochondrial Ca2+ concentrations in live cells: quantification methods and discrepancies

FEBS Lett. 2019 Jul;593(13):1528-1541. doi: 10.1002/1873-3468.13427. Epub 2019 May 18.

Abstract

Intracellular Ca2+ signaling controls numerous cellular functions. Mitochondria respond to cytosolic Ca2+ changes by adapting mitochondrial functions and, in some cell types, shaping the spatiotemporal properties of the cytosolic Ca2+ signal. Numerous methods have been developed to specifically and quantitatively measure the mitochondrial-free Ca2+ concentrations ([Ca2+ ]m ), but there are still significant discrepancies in the calculated absolute values of [Ca2+ ]m in stimulated live cells. These discrepancies may be due to the distinct properties of the methods used to measure [Ca2+ ]m , the calcium-free/bound ratio, and the cell-type and stimulus-dependent Ca2+ dynamics. Critical processes happening in the mitochondria, such as ATP generation, ROS homeostasis, and mitochondrial permeability transition opening, depend directly on the [Ca2+ ]m values. Thus, precise determination of absolute [Ca2+ ]m values is imperative for understanding Ca2+ signaling. This review summarizes the reported calibrated [Ca2+ ]m values in many cell types and discusses the discrepancies among these values. Areas for future research are also proposed.

Keywords: fluorescent Ca2+ indicators; genetically encoded Ca2+ indicators; live cells; mitochondrial Ca2+ concentrations.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Survival
  • Energy Metabolism
  • Humans
  • Mitochondria / metabolism*

Substances

  • Calcium