PubAg

Main content area

Muscle activity prevents the uncoupling of mitochondria from Ca2+ Release Units induced by ageing and disuse

Author:
Pietrangelo, Laura, Michelucci, Antonio, Ambrogini, Patrizia, Sartini, Stefano, Guarnier, Flavia A., Fusella, Aurora, Zamparo, Ilaria, Mammucari, Cristina, Protasi, Feliciano, Boncompagni, Simona
Source:
Archives of biochemistry and biophysics 2019 v.663 pp. 22-33
ISSN:
0003-9861
Subject:
Western blotting, adults, calcium, calcium signaling, electron microscopy, exercise, mice, mitochondria, muscles, oxidative stress, rats
Abstract:
In fast-twitch fibers from adult mice Ca2+ release units (CRUs, i.e. intracellular junctions of excitation-contraction coupling), and mitochondria are structurally linked to each other by small strands, named tethers. We recently showed that aging causes separation of a fraction of mitochondria from CRUs and a consequent impairment of the Ca2+ signaling between the two organelles. However, whether the uncoupling of mitochondria from CRUs is the result of aging per-se or the consequence of reduced muscle activity remains still unclear. Here we studied the association between mitochondria and CRUs: in a) extensor digitorum longus (EDL) muscles from 2 years old mice, either sedentary or trained for 1 year in wheel cages; and b) denervated EDL muscles from adult mice and rats. We analyzed muscle samples using a combination of structural (confocal and electron microscopy), biochemical (assessment of oxidative stress via western blot), and functional (ex-vivo contractile properties, and mitochondrial Ca2+ uptake) experimental procedures. The results collected in structural studies indicate that: a) ageing and denervation result in partial uncoupling between mitochondria and CRUs; b) exercise either maintains (in old mice) or restores (in transiently denervated rats) the association between the two organelles. Functional studies supported the hypothesis that CRU-mitochondria coupling is important for mitochondrial Ca2+ uptake, optimal force generation, and muscle performance. Taken together our results indicate that muscle activity maintains/improves proper association between CRUs and mitochondria.
Agid:
6263927