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Accepted Manuscript
Research Article
Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila
Alba Delrio-Lorenzo, Jonathan Rojo-Ruiz, María Teresa Alonso, Javier García-Sancho
Journal of Cell Science 2020 : jcs.240879 doi: 10.1242/jcs.240879 Published 31 January 2020
Alba Delrio-Lorenzo
Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), c/ Sanz y Forés 3, 47003 Valladolid, Spain
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Jonathan Rojo-Ruiz
Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), c/ Sanz y Forés 3, 47003 Valladolid, Spain
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María Teresa Alonso
Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), c/ Sanz y Forés 3, 47003 Valladolid, Spain
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Javier García-Sancho
Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), c/ Sanz y Forés 3, 47003 Valladolid, Spain
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  • For correspondence: jgsancho@ibgm.uva.es
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Abstract

Sarcopenia, the loss of muscle mass and strength associated to age, has been linked to impairment of the cytosolic Ca2+ peak that triggers muscle contraction, but mechanistic details remain unknown. Here we explore the hypothesis that a reduction in sarcoplasmic reticulum Ca2+ concentration ([Ca2+]SR) is at the origin of this loss of Ca2+ homeostasis. We engineered Drosophila melanogaster to express the Ca2+ indicator GAP3 targeted to muscle SR, and we developed a new method to calibrate the signal into [Ca2+]SR in vivo. [Ca2+]SR dropped with age from ∼600 µM down to 50 µM in close correlation to muscle function, which declined monotonically when [Ca2+]SR was <400 µM. [Ca2+]SR results from the pump-leak steady-state at the SR membrane. However, changes in expression of the SERCA pump and of the ryanodine receptor leak, were too modest to explain the large changes seen in [Ca2+]SR. Instead, these changes are compatible with increased leakiness through the ryanodine receptor as the main determinant of the [Ca2+]SR decline in aging muscle. In contrast, there were no changes in endoplasmic reticulum [Ca2+] with age in brain neurons.

  • Received October 21, 2019.
  • Accepted January 24, 2020.
  • © 2020. Published by The Company of Biologists Ltd
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Keywords

  • Aging
  • Sarcopenia
  • Calcium homeostasis
  • Calcium imaging
  • Sarcoplasmic reticulum
  • Endoplasmic reticulum
  • Sarco/endoplasmic reticulum calcium ATPase (SERCA)
  • Ryanodine receptor
  • Drosophila melanogaster
  • Fly

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Accepted Manuscript
Research Article
Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila
Alba Delrio-Lorenzo, Jonathan Rojo-Ruiz, María Teresa Alonso, Javier García-Sancho
Journal of Cell Science 2020 : jcs.240879 doi: 10.1242/jcs.240879 Published 31 January 2020
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Accepted Manuscript
Research Article
Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila
Alba Delrio-Lorenzo, Jonathan Rojo-Ruiz, María Teresa Alonso, Javier García-Sancho
Journal of Cell Science 2020 : jcs.240879 doi: 10.1242/jcs.240879 Published 31 January 2020

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