Remodeling of calcium handling in skeletal muscle through PGC-1?: impact on force, fatigability, and fiber type

Summermatter, Serge; Thurnheer, Raphael; Santos, Gesa; Mosca, Barbara; Baum, Oliver; Treves, Susan; Hoppeler, Hans; Zorzato, Francesco; Handschin, Christoph (2012). Remodeling of calcium handling in skeletal muscle through PGC-1?: impact on force, fatigability, and fiber type. American journal of physiology - cell physiology, 302(1), C88-99. Bethesda, Md.: American Physiological Society 10.1152/ajpcell.00190.2011

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Regular endurance exercise remodels skeletal muscle, largely through the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α promotes fiber type switching and resistance to fatigue. Intracellular calcium levels might play a role in both adaptive phenomena, yet a role for PGC-1α in the adaptation of calcium handling in skeletal muscle remains unknown. Using mice with transgenic overexpression of PGC-1α, we now investigated the effect of PGC-1α on calcium handling in skeletal muscle. We demonstrate that PGC-1α induces a quantitative reduction in calcium release from the sarcoplasmic reticulum by diminishing the expression of calcium-releasing molecules. Concomitantly, maximal muscle force is reduced in vivo and ex vivo. In addition, PGC-1α overexpression delays calcium clearance from the myoplasm by interfering with multiple mechanisms involved in calcium removal, leading to higher myoplasmic calcium levels following contraction. During prolonged muscle activity, the delayed calcium clearance might facilitate force production in mice overexpressing PGC-1α. Our results reveal a novel role of PGC-1α in altering the contractile properties of skeletal muscle by modulating calcium handling. Importantly, our findings indicate PGC-1α to be both down- as well as upstream of calcium signaling in this tissue. Overall, our findings suggest that in the adaptation to chronic exercise, PGC-1α reduces maximal force, increases resistance to fatigue, and drives fiber type switching partly through remodeling of calcium transients, in addition to promoting slow-type myofibrillar protein expression and adequate energy supply.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
UniBE Contributor:	Baum, Oliver, Hoppeler, Hans-Heinrich
ISSN:	0363-6143
Publisher:	American Physiological Society
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:17
Last Modified:	05 Dec 2022 14:04
Publisher DOI:	10.1152/ajpcell.00190.2011
PubMed ID:	21918181
Web of Science ID:	000298374100012
URI:	https://boris.unibe.ch/id/eprint/5116 (FactScience: 209834)