Fig 2. Role of Ca²⁺ signaling during NLRP3 inflammasome activation.

Ca²⁺ and cAMP may bind directly to the NLRP3 inflammasome complex to positively and negatively regulate assembly and/or activation respectively, such that the balance of Ca²⁺ and cAMP signaling determines the outcome of inflammasome activation (left). Alternatively, mitochondrial Ca²⁺ uptake (via ER Ca²⁺ release channels and mitochondrial MCU) can lead to Ca²⁺ overload and associated mitochondrial destabilization, including mROS production and induction of MPT, thus facilitating cardiolipin externalization and mtDNA release (right).