Intracellular to Interorgan Mitochondrial Communication in Striated Muscle in Health and Disease

Neoma T Boardman, Giulia Trani, Marco Scalabrin, Vanina Romanello, Rob C I Wüst

Mitochondria both sense biochemical and energetic input in addition to communicating signals regarding the energetic state of the cell. Increasingly, these signaling organelles are key for regulating different cell functions. This review summarizes recent advances in mitochondrial communication in striated muscle, with specific focus on the processes by which mitochondria communicate with each other, other organelles and across distant organ systems. Inter-mitochondrial communication in striated muscle is mediated via conduction of the mitochondrial membrane potential to adjacent mitochondria, physical interactions, mitochondrial fusion or fission and via nannotunnels, allowing for the exchange of proteins, mitochondrial DNA, nucleotides, and peptides. Within striated muscle cells, mitochondria-organelle communication can modulate overall cell function. The various mechanisms in which mitochondria communicate mitochondrial fitness to the rest of the body suggest that extracellular mitochondrial signaling is key during health and disease. Whereas mitochondrial-derived vesicles might excrete mitochondrial-derived endocrine compounds, stimulation of mitochondrial stress can lead to the release of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) into the circulation to modulate whole-body physiology. Circulating mitochondrial DNA are well-known alarmins that trigger the immune system and may help to explain low-grade inflammation in various chronic diseases. Impaired mitochondrial function and communication are central in common heart and skeletal muscle pathologies, including cardiomyopathies, insulin resistance, and sarcopenia. Lastly, important new advances in research in mitochondrial endocrinology, communication, medical horizons and translational aspects are discussed.