Parvalbumin affects skeletal muscle trophism through modulation of mitochondrial calcium uptake

• Main Authors: Gaia Butera, Denis Vecellio Reane, Marta Canato, Laura Pietrangelo, Simona Boncompagni, Feliciano Protasi, Rosario Rizzuto, Carlo Reggiani, Anna Raffaello
• Format: Article
• Language: English
• Published: Elsevier 2021-05-01
• Series: Cell Reports
• Subjects: calcium buffer; mitochondria; skeletal muscle
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124721004204

Summary: Parvalbumin (PV) is a cytosolic Ca2+-binding protein highly expressed in fast skeletal muscle, contributing to an increased relaxation rate. Moreover, PV is an “atrogene” downregulated in most muscle atrophy conditions. Here, we exploit mice lacking PV to explore the link between the two PV functions. Surprisingly, PV ablation partially counteracts muscle loss after denervation. Furthermore, acute PV downregulation is accompanied by hypertrophy and upregulation by atrophy. PV ablation has a minor impact on sarcoplasmic reticulum but is associated with increased mitochondrial Ca2+ uptake, mitochondrial size and number, and contacts with Ca2+ release sites. Mitochondrial calcium uniporter (MCU) silencing abolishes the hypertrophic effect of PV ablation, suggesting that mitochondrial Ca2+ uptake is required for hypertrophy. In turn, an increase of mitochondrial Ca2+ is required to enhance expression of the pro-hypertrophy gene PGC-1α4, whose silencing blocks hypertrophy due to PV ablation. These results reveal how PV links cytosolic Ca2+ control to mitochondrial adaptations, leading to muscle mass regulation.