RT info:eu-repo/semantics/article
T1 Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila
A1 Río Lorenzo, Alba del
A1 Rojo Ruiz, Jonathan
A1 Alonso Alonso, María Teresa
A1 García-Sancho Martín, Francisco Javier
K1 Calcium homeostasis
K1 Homeostasis del calcio
K1 Drosophila melanogaster
K1 Endoplasmic reticulum
K1 Retículo endoplasmático
K1 Sarcopenia
K1 Sarcoplasmic reticulum
K1 Retículo sarcoplasmático
AB Sarcopenia, the loss of muscle mass and strength associated with 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 (SR) 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 fell with age from ∼600 µM to 50 µM in close correlation with 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 sarco/endoplasmic reticulum Ca2+-ATPase (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.
PB The Company of Biologists
SN 1477-9137
YR 2020
FD 2020
LK http://uvadoc.uva.es/handle/10324/45019
UL http://uvadoc.uva.es/handle/10324/45019
LA eng
NO Journal of Cell Science, 2020, vol. 133, n. 6. 9 p.
NO Producción Científica
DS UVaDOC
RD 12-jul-2024