Cell Reports (Mar 2024)
Flvcr1a deficiency promotes heme-based energy metabolism dysfunction in skeletal muscle
- 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 Geninatti Crich,
- Chiara Riganti,
- Yvan Torrente,
- Emanuela Tolosano
Affiliations
- Miriam Mistretta
- Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Veronica Fiorito
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
- Anna Lucia Allocco
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
- Giorgia Ammirata
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
- Myriam Y. Hsu
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
- Sabrina Digiovanni
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Oncology, University of Torino, 10126 Torino, Italy
- Marzia Belicchi
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano, 20122 Milan, Italy
- Laura Napoli
- Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Michela Ripolone
- Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Elena Trombetta
- Flow Cytometry Service, Clinical Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- PierLuigi Mauri
- National Research Council of Italy, Proteomics and Metabolomics Unit, Institute for Biomedical Technologies, ITB-CNR, 20054 Segrate, Milan, Italy; Clinical Proteomics Laboratory c/o ITB-CNR, CNR.Biomics Infrastructure, ElixirNextGenIT, 20054 Segrate, Milan, Italy
- Andrea Farini
- Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Mirella Meregalli
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano, 20122 Milan, Italy
- Chiara Villa
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano, 20122 Milan, Italy
- Paolo Ettore Porporato
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
- Barbara Miniscalco
- Department of Veterinary Sciences, University of Torino, 10095 Grugliasco, Torino, Italy
- Simonetta Geninatti Crich
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
- Chiara Riganti
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Oncology, University of Torino, 10126 Torino, Italy
- Yvan Torrente
- Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Dino Ferrari Centre, Università degli Studi di Milano, 20122 Milan, Italy; Corresponding author
- Emanuela Tolosano
- Molecular Biotechnology Center (MBC) “Guido Tarone”, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 3
p. 113854
Abstract
Summary: 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.
