Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing
Proper skeletal muscle function is controlled by intracellular Ca<sup>2+</sup> concentration and by efficient production of energy (ATP), which, in turn, depend on: (a) the release and re-uptake of Ca<sup>2+</sup> from sarcoplasmic-reticulum (SR) during excitation–contraction...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Feliciano Protasi Laura Pietrangelo Simona Boncompagni |
| author_facet | Feliciano Protasi Laura Pietrangelo Simona Boncompagni |
| author_sort | Feliciano Protasi |
| collection | DOAJ |
| description | Proper skeletal muscle function is controlled by intracellular Ca<sup>2+</sup> concentration and by efficient production of energy (ATP), which, in turn, depend on: (a) the release and re-uptake of Ca<sup>2+</sup> from sarcoplasmic-reticulum (SR) during excitation–contraction (EC) coupling, which controls the contraction and relaxation of sarcomeres; (b) the uptake of Ca<sup>2+</sup> into the mitochondrial matrix, which stimulates aerobic ATP production; and finally (c) the entry of Ca<sup>2+</sup> from the extracellular space via store-operated Ca<sup>2+</sup> entry (SOCE), a mechanism that is important to limit/delay muscle fatigue. Abnormalities in Ca<sup>2+</sup> handling underlie many physio-pathological conditions, including dysfunction in ageing. The specific focus of this review is to discuss the importance of the proper architecture of organelles and membrane systems involved in the mechanisms introduced above for the correct skeletal muscle function. We reviewed the existing literature about EC coupling, mitochondrial Ca<sup>2+</sup> uptake, SOCE and about the structural membranes and organelles deputed to those functions and finally, we summarized the data collected in different, but complementary, projects studying changes caused by denervation and ageing to the structure and positioning of those organelles: a. denervation of muscle fibers—an event that contributes, to some degree, to muscle loss in ageing (known as sarcopenia)—causes misplacement and damage: (i) of membrane structures involved in EC coupling (calcium release units, CRUs) and (ii) of the mitochondrial network; b. sedentary ageing causes partial disarray/damage of CRUs and of calcium entry units (CEUs, structures involved in SOCE) and loss/misplacement of mitochondria; c. functional electrical stimulation (FES) and regular exercise promote the rescue/maintenance of the proper architecture of CRUs, CEUs, and of mitochondria in both denervation and ageing. All these structural changes were accompanied by related functional changes, i.e., loss/decay in function caused by denervation and ageing, and improved function following FES or exercise. These data suggest that the integrity and proper disposition of intracellular organelles deputed to Ca<sup>2+</sup> handling and aerobic generation of ATP is challenged by inactivity (or reduced activity); modifications in the architecture of these intracellular membrane systems may contribute to muscle dysfunction in ageing and sarcopenia. |
| first_indexed | 2024-03-10T10:36:33Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
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| spelling | doaj.art-db1d6202a6ab43aeb402a2121fe9086e2023-11-21T23:17:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212619510.3390/ijms22126195Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in AgeingFeliciano Protasi0Laura Pietrangelo1Simona Boncompagni2CAST, Center for Advanced Studies and Technology, University G. d’Annunzio of Chieti-Pescara, I-66100 Chieti, ItalyCAST, Center for Advanced Studies and Technology, University G. d’Annunzio of Chieti-Pescara, I-66100 Chieti, ItalyCAST, Center for Advanced Studies and Technology, University G. d’Annunzio of Chieti-Pescara, I-66100 Chieti, ItalyProper skeletal muscle function is controlled by intracellular Ca<sup>2+</sup> concentration and by efficient production of energy (ATP), which, in turn, depend on: (a) the release and re-uptake of Ca<sup>2+</sup> from sarcoplasmic-reticulum (SR) during excitation–contraction (EC) coupling, which controls the contraction and relaxation of sarcomeres; (b) the uptake of Ca<sup>2+</sup> into the mitochondrial matrix, which stimulates aerobic ATP production; and finally (c) the entry of Ca<sup>2+</sup> from the extracellular space via store-operated Ca<sup>2+</sup> entry (SOCE), a mechanism that is important to limit/delay muscle fatigue. Abnormalities in Ca<sup>2+</sup> handling underlie many physio-pathological conditions, including dysfunction in ageing. The specific focus of this review is to discuss the importance of the proper architecture of organelles and membrane systems involved in the mechanisms introduced above for the correct skeletal muscle function. We reviewed the existing literature about EC coupling, mitochondrial Ca<sup>2+</sup> uptake, SOCE and about the structural membranes and organelles deputed to those functions and finally, we summarized the data collected in different, but complementary, projects studying changes caused by denervation and ageing to the structure and positioning of those organelles: a. denervation of muscle fibers—an event that contributes, to some degree, to muscle loss in ageing (known as sarcopenia)—causes misplacement and damage: (i) of membrane structures involved in EC coupling (calcium release units, CRUs) and (ii) of the mitochondrial network; b. sedentary ageing causes partial disarray/damage of CRUs and of calcium entry units (CEUs, structures involved in SOCE) and loss/misplacement of mitochondria; c. functional electrical stimulation (FES) and regular exercise promote the rescue/maintenance of the proper architecture of CRUs, CEUs, and of mitochondria in both denervation and ageing. All these structural changes were accompanied by related functional changes, i.e., loss/decay in function caused by denervation and ageing, and improved function following FES or exercise. These data suggest that the integrity and proper disposition of intracellular organelles deputed to Ca<sup>2+</sup> handling and aerobic generation of ATP is challenged by inactivity (or reduced activity); modifications in the architecture of these intracellular membrane systems may contribute to muscle dysfunction in ageing and sarcopenia.https://www.mdpi.com/1422-0067/22/12/6195Ca<sup>2+</sup> entry unit (CEU)Ca<sup>2+</sup> release unit (CRU)excitation–contraction (EC) couplingmitochondriasarcoplasmic-reticulum (SR)store-operated Ca<sup>2+</sup> entry (SOCE) |
| spellingShingle | Feliciano Protasi Laura Pietrangelo Simona Boncompagni Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing International Journal of Molecular Sciences Ca<sup>2+</sup> entry unit (CEU) Ca<sup>2+</sup> release unit (CRU) excitation–contraction (EC) coupling mitochondria sarcoplasmic-reticulum (SR) store-operated Ca<sup>2+</sup> entry (SOCE) |
| title | Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing |
| title_full | Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing |
| title_fullStr | Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing |
| title_full_unstemmed | Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing |
| title_short | Improper Remodeling of Organelles Deputed to Ca<sup>2+</sup> Handling and Aerobic ATP Production Underlies Muscle Dysfunction in Ageing |
| title_sort | improper remodeling of organelles deputed to ca sup 2 sup handling and aerobic atp production underlies muscle dysfunction in ageing |
| topic | Ca<sup>2+</sup> entry unit (CEU) Ca<sup>2+</sup> release unit (CRU) excitation–contraction (EC) coupling mitochondria sarcoplasmic-reticulum (SR) store-operated Ca<sup>2+</sup> entry (SOCE) |
| url | https://www.mdpi.com/1422-0067/22/12/6195 |
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