Use of aequorin-based indicators for monitoring Ca2+in acidic organelles*

Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified.

Automated summary

Evidence has shown that acidic organelles can accumulate and release Ca2+ upon cell activation. Monitoring the dynamics of Ca2+ in these compartments is crucial for understanding their physiopathological aspects. Bioluminescent GECIs have advantages in acidic compartments due to their low pH sensitivity, low background noise, no phototoxicity, no photobleaching, high dynamic range, and tunable affinity. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments and highlights the need for more measurements in highly acidic compartments.