Figure 4.

Mitochondrial Ca²⁺. Mitochondria are densely packed in the cardiomyocyte being aligned along the myofilaments as bricks. Their Ca²⁺ uptake sites are closely localized to the junctional sarcoplasmic reticulum (SR) and a microdomain of elevated Ca²⁺ generated by SR Ca²⁺ release via RyRs. Ca²⁺ enters the mitochondria through the voltage-gated anion channel (VDAC) of the outer mitochondrial membrane and the mitochondrial Ca²⁺ uniporter (MCU) of the inner mitochondrial membrane. Ca²⁺ acts at multiple sites in the electron transport chain and tricarboxylic acid (TCA) cycle to modulate mitochondrial metabolism and ATP production. Ca²⁺ is extruded from the mitochondria through a Na⁺/Li⁺/Ca²⁺ exchanger (NCXL) and/or a Ca²⁺/H⁺ exchanger (mHCX).