Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU

http://www.cell.com/cell-reports/pdf/S2211-1247(17)30213-9.pdf

Paillard M, Csordás G, Szanda G, Golenár T, Debattisti V, Bartok A, Wang N, Moffat C, Seifert EL, Spät A, Hajnóczky G

Mitochondrial respiration is sensitive to the concentration of calcium in the cytoplasm, acting as an important control mechanism of respiration rate. It is known that different tissues have different responses to the presence of calcium. For instance, in the liver, calcium oscillations in the cytoplasm tend to be low frequency and are effectively propagated to intra-mitochondrial calcium concentrations. However, in the heart, oscillations are high frequency and are integrated into a more continuous intra-mitochondrial calcium signal.

Here, the authors investigated the difference in mitochondrial response to calcium concentration in different tissues by measuring the relative stoichiometry of two protein components of the mitochondrial calcium uniporter: MCU (a calcium pore unit) and MICU1 (a Calcium-sensing regulator). The authors found that, in heart tissue, a low MICU1 to MCU ratio is present, which results in a low cytoplasmic calcium threshold for mitochondrial accumulation of calcium, relative to liver tissue. Furthermore, heart tissue displayed a more shallow response curve to cytoplasmic calcium, suggesting lower cooperativity in cardiac tissue, relative to liver tissue. Therefore, the ratio of MICU1:MCU controls the tissue-specific response to cytoplasmic calcium.