Sarcoplasmic reticulum and calcium signaling in muscle cells: Homeostasis and disease

The sarco/endoplasmic reticulum is an extensive, dynamic and heterogeneous membranous network that fulfills multiple homeostatic functions. Among them, it compartmentalizes, stores and releases calcium within the intracellular space. In the case of muscle cells, calcium released from the sarco/endoplasmic reticulum in the vicinity of the contractile machinery induces cell contraction. Furthermore, sarco/endoplasmic reticulum-derived calcium also regulates gene transcription in the nucleus, energy metabolism in mitochondria and cytosolic signaling pathways. These diverse and overlapping processes require a highly complex fine-tuning that the sarco/endoplasmic reticulum provides by means of its numerous tubules and cisternae, specialized domains and contacts with other organelles. The sarco/endoplasmic reticulum also possesses a rich calcium-handling machinery, functionally coupled to both contraction-inducing stimuli and the contractile apparatus. Such is the importance of the sarco/endoplasmic reticulum for muscle cell physiology, that alterations in its structure, function or its calcium-handling machinery are intimately associated with the development of cardiometabolic diseases. Cardiac hypertrophy, insulin resistance and arterial hypertension are age-related pathologies with a common mechanism at the muscle cell level: the accumulation of damaged proteins at the sarco/endoplasmic reticulum induces a stress response condition termed endoplasmic reticulum stress, which impairs proper organelle function, ultimately leading to pathogenesis.Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) FONDAP 15130011 FONDECYT 1190743 1161156 1200490 Programa de Investigación Asociativa (PIA)-CONICYT 172066 Installation Program 77170004 2017 University of Chile FIDA/ABCvital 02-2018 U-Inicia UI-006-19 U-Redes Generacion VID G_2018-35 International Centre for Genetic Engineering and Biotechnology (ICGEB) CRP/CHL18-0