Intracellular Membrane Contact Sites in Skeletal Muscle Cells

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Intracellular organelles are common to eukaryotic cells and provide physical support for the assembly of specialized compartments. In skeletal muscle fibers, the largest intracellular organelle is the sarcoplasmic reticulum, a specialized form of the endoplasmic reticulum primarily devoted to Ca2+ storage and release for muscle contraction. Occupying about 10% of the total cell volume, the sarcoplasmic reticulum forms multiple membrane contact sites, some of which are unique to skeletal muscle. These contact sites primarily involve the plasma membrane; among these, specialized membrane contact sites between the transverse tubules and the terminal cisternae of the sarcoplasmic reticulum form triads. Triads are skeletal muscle-specific contact sites where Ca2+ channels and regulatory proteins assemble to form the so-called calcium release complex. Additionally, the sarcoplasmic reticulum contacts mitochondria to enable a more precise regulation of Ca2+ homeostasis and energy metabolism. The sarcoplasmic reticulum and the plasma membrane also undergo dynamic remodeling to allow Ca2+ entry from the extracellular space and replenish the stores. This process involves the formation of dynamic membrane contact sites called Ca2+ Entry Units. This review explores the key processes in biogenesis and assembly of intracellular membrane contact sites as well as the membrane remodeling that occurs in response to muscle fatigue.