Skeletal muscle mitochondria are placed in close proximity of the sarcoplasmic reticulum (SR), the main intracellular Ca2 + store. During muscle activity, excitation of sarcolemma and of T-tubule triggers the release of Ca2 + from the SR initiating myofiber contraction. The rise in cytosolic Ca2 + determines the opening of the mitochondrial calcium uniporter (MCU), the highly selective channel of the inner mitochondrial membrane (IMM), causing a robust increase in mitochondrial Ca2 + uptake. The Ca2 +-dependent activation of TCA cycle enzymes increases the synthesis of ATP required for SERCA activity. Thus, Ca2 + is transported back into the SR and cytosolic [Ca2 +] returns to resting levels eventually leading to muscle relaxation. In recent years, thanks to the molecular identification of MCU complex components, the role of mitochondrial Ca2 + uptake in the pathophysiology of skeletal muscle has been uncovered. In this chapter, we will introduce the reader to a general overview of mitochondrial Ca2 + accumulation. We will tackle the key molecular players and the cellular and pathophysiological consequences of mitochondrial Ca2 + dyshomeostasis. In the second part of the chapter, we will discuss novel findings on the physiological role of mitochondrial Ca2 + uptake in skeletal muscle. Finally, we will examine the involvement of mitochondrial Ca2 + signaling in muscle diseases.

The mitochondrial calcium homeostasis orchestra plays its symphony: Skeletal muscle is the guest of honor

Gherardi G.;De Mario A.;Mammucari C.
2021

Abstract

Skeletal muscle mitochondria are placed in close proximity of the sarcoplasmic reticulum (SR), the main intracellular Ca2 + store. During muscle activity, excitation of sarcolemma and of T-tubule triggers the release of Ca2 + from the SR initiating myofiber contraction. The rise in cytosolic Ca2 + determines the opening of the mitochondrial calcium uniporter (MCU), the highly selective channel of the inner mitochondrial membrane (IMM), causing a robust increase in mitochondrial Ca2 + uptake. The Ca2 +-dependent activation of TCA cycle enzymes increases the synthesis of ATP required for SERCA activity. Thus, Ca2 + is transported back into the SR and cytosolic [Ca2 +] returns to resting levels eventually leading to muscle relaxation. In recent years, thanks to the molecular identification of MCU complex components, the role of mitochondrial Ca2 + uptake in the pathophysiology of skeletal muscle has been uncovered. In this chapter, we will introduce the reader to a general overview of mitochondrial Ca2 + accumulation. We will tackle the key molecular players and the cellular and pathophysiological consequences of mitochondrial Ca2 + dyshomeostasis. In the second part of the chapter, we will discuss novel findings on the physiological role of mitochondrial Ca2 + uptake in skeletal muscle. Finally, we will examine the involvement of mitochondrial Ca2 + signaling in muscle diseases.
International Review of Cell and Molecular Biology
9780128240342
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3412235
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