3D Visualization of Mitochondrial Solid-Phase Calcium Stores in Whole Cells

Elife. 2017 Nov 6;6:e29929. doi: 10.7554/eLife.29929.


The entry of calcium into mitochondria is central to metabolism, inter-organelle communication, and cell life/death decisions. Long-sought transporters involved in mitochondrial calcium influx and efflux have recently been identified. To obtain a unified picture of mitochondrial calcium utilization, a parallel advance in understanding the forms and quantities of mitochondrial calcium stores is needed. We present here the direct 3D visualization of mitochondrial calcium in intact mammalian cells using cryo-scanning transmission electron tomography (CSTET). Amorphous solid granules containing calcium and phosphorus were pervasive in the mitochondrial matrices of a variety of mammalian cell types. Analysis based on quantitative electron scattering revealed that these repositories are equivalent to molar concentrations of dissolved ions. These results demonstrate conclusively that calcium buffering in the mitochondrial matrix in live cells occurs by phase separation, and that solid-phase stores provide a major ion reservoir that can be mobilized for bioenergetics and signaling.

Keywords: calcium; cell biology; cryo-STEM microscopy; human; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / analysis*
  • Cell Line
  • Cryoelectron Microscopy
  • Electron Microscope Tomography
  • Humans
  • Imaging, Three-Dimensional*
  • Mice
  • Mitochondria / chemistry*
  • Phosphorus / analysis


  • Phosphorus
  • Calcium

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.