The MCU complex in cell death

Abstract

During the 60s, the notion that positively charged Ca²⁺ ions are rapidly accumulated in energized mitochondria has been first established. In the following decades, mitochondrial Ca²⁺ homeostasis was shown to control cell metabolism, cell survival and other cell-specific functions through different mechanism. However, the molecular identity of the molecules controlling this process remained a mystery until just few years ago, when both mitochondrial Ca²⁺ uptake and release systems were genetically dissected. This finally opened the possibility to develop genetic model to directly test the contribution of mitochondrial Ca²⁺ homeostasis to cellular functions. Although the picture is still far from being clear, we here summarize and critically evaluate the current knowledge on how mitochondrial Ca²⁺ handling controls cell death.

Keywords: Calcium; Cell death; MCU; MCU complex; Mitochondria.