Crosstalk between Calcium and ROS in Pathophysiological Conditions

Figure 1

Schematic representation of the mitochondrial Ca²⁺ uniporter (MCU) complex. The MCU complex is composed by pore-forming subunits (that comprise the channel subunits MCU, the dominant-negative subunits MCUb, and the transmembrane regulator EMRE) and regulatory subunits (MICU1 and MICU2). MICU1 and MICU2 sense, through EF-hand domains, the increase of Ca²⁺ levels in the intermembrane space (IMS). In resting conditions (on the left), MICU1-MICU2 heterodimers act as gatekeeper of the channel, thus preventing Ca²⁺ vicious cycling and mitochondrial matrix overload. Increases in calcium concentration as a result of cell stimulation (on the right) not only release the inhibitory function of the MICU1-MICU2 heterodimers but also further stimulate MCU channel opening, ensuring the prompt response of mitochondrial metabolism to cell stimulation.

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