Figure 8.

Rewiring of the Ca²⁺-signalling pathways triggering different cellular programmes. (a) General scheme of rewiring dependent on transmitochondrial Ca²⁺ transport. If the mtCU and the mNCX are active, elevated Ca²⁺ ions undergo periodic fluctuations and stimulate Ca²⁺ oscillation-dependent proteins (pattern I), whereas cytosolic Ca²⁺ retention will keep these targets inactive (pattern II; left side). Deficiency in mitochondrial transport will favour stimulation of pattern II at the expense of pattern I (right side). (b) Proposed scheme of rewiring in Th differentiation. Intense transmitochondrial Ca²⁺ transport leads to strong NFAT activation and bias towards Th1 lymphocytes and suppression of Th2 stemming (left side), whereas diminished mtCU in T cells will be accompanied by a PKC-dependent stimulation of NADPH oxidase, which requires accumulation of intracellular Ca²⁺ leading to Th2 differentiation (right side).