Figure 2. Schematic representation of the dependence of microdomain Ca²⁺ signaling on mitochondrial location with respect to the site of Ca²⁺ release.

(Left) Model of ER-mitochondrial localization and degree of microdomain Ca²⁺ signaling during IP₃-mediated Ca²⁺ release (Merkwirth and Langer, 2008). When the mitochondrion is located only 10 nm from the point source of Ca²⁺ release, significant microdomain Ca²⁺ signaling occurs and mitochondrial Ca²⁺ uptake is driven by a large but rapidly dissipating local Ca²⁺ signal. Figure adapted from Cell, 135(7), Merkwirth and Langer, Mitofusin 2 builds a bridge between ER and mitochondria, 1165−1167, 2008, with permission from Elsevier. (Right) Model of SR-mitochondrial localization and degree of microdomain Ca²⁺ signaling during RyR1-mediated dependent Ca²⁺ release in adult mammalian skeletal muscle. Since CRU-associated mitochondria are located 130 nm from the point source of Ca²⁺ release (Boncompagni et al., 2009), limited microdomain signaling occurs and mitochondrial Ca²⁺ uptake is driven largely by the global myoplasmic Ca²⁺ signal.