The Evolution of the Mitochondria-to-Calcium Release Units Relationship in Vertebrate Skeletal Muscles

The spatial relationship between mitochondria and the membrane systems, more specifically the calcium release units (CRUs) of skeletal muscle, is of profound functional significance. CRUs are the sites at which Ca2+ is released from the sarcoplasmic reticulum during muscle activation. Close mitochondrion-CRU proximity allows the organelles to take up Ca2+ and thus stimulate aerobic metabolism. Skeletal muscles of most mammals display an extensive, developmentally regulated, close mitochondrion-CRU association, fostered by tethering links between the organelles. A comparative look at the vertebrate subphylum however shows that this specific association is only present in the higher vertebrates (mammals). Muscles in all other vertebrates, even if capable of fast activity, rely on a less precise and more limited mitochondrion-CRU proximity, despite some tethering connections. This is most evident in fish muscles. Clustering of free subsarcolemmal mitochondria in proximity of capillaries is also more frequently achieved in mammalian than in other vertebrates

Evolution of skeletal type e–c coupling: a novel means of controlling calcium delivery

The functional separation between skeletal and cardiac muscles, which occurs at the threshold between vertebrates and invertebrates, involves the evolution of separate contractile and control proteins for the two types of striated muscles, as well as separate mechanisms of contractile activation. The functional link between electrical excitation of the surface membrane and activation of the contractile material (known as excitation–contraction [e–c] coupling) requires the interaction between a voltage sensor in the surface membrane, the dihydropyridine receptor (DHPR), and a calcium release channel in the sarcoplasmic reticulum, the ryanodine receptor (RyR). Skeletal and cardiac muscles have different isoforms of the two proteins and present two structurally and functionally distinct modes of interaction