Flvcr1a deficiency promotes heme-based energy metabolism dysfunction in skeletal muscle

Flvcr1a 缺乏导致骨骼肌血红素能量代谢功能障碍

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作者:Miriam Mistretta, Veronica Fiorito, Anna Lucia Allocco, Giorgia Ammirata, Myriam Y Hsu, Sabrina Digiovanni, Marzia Belicchi, Laura Napoli, Michela Ripolone, Elena Trombetta, PierLuigi Mauri, Andrea Farini, Mirella Meregalli, Chiara Villa, Paolo Ettore Porporato, Barbara Miniscalco, Simonetta Geninat

Abstract

The definition of cell metabolic profile is essential to ensure skeletal muscle fiber heterogeneity and to achieve a proper equilibrium between the self-renewal and commitment of satellite stem cells. Heme sustains several biological functions, including processes profoundly implicated with cell metabolism. The skeletal muscle is a significant heme-producing body compartment, but the consequences of impaired heme homeostasis on this tissue have been poorly investigated. Here, we generate a skeletal-muscle-specific feline leukemia virus subgroup C receptor 1a (FLVCR1a) knockout mouse model and show that, by sustaining heme synthesis, FLVCR1a contributes to determine the energy phenotype in skeletal muscle cells and to modulate satellite cell differentiation and muscle regeneration.

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