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.