Metabolomic fingerprinting of renal disease progression in Bardet-Biedl syndrome reveals mitochondrial dysfunction in kidney tubular cells
Emanuela Marchese,
Marianna Caterino,
Davide Viggiano,
Armando Cevenini,
Salvatore Tolone,
Ludovico Docimo,
Valentina Di Iorio,
Francesca Del Vecchio Blanco,
Roberta Fedele,
Francesca Simonelli,
Alessandra Perna,
Vincenzo Nigro,
Giovambattista Capasso,
Margherita Ruoppolo,
Miriam Zacchia
Affiliations
Emanuela Marchese
Department of Mental, Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Largo Madonna Delle Grazie, 1 80138 Naples, Italy; Ceinge, Advanced Biotechnology, Naples, Italy
Marianna Caterino
Ceinge, Advanced Biotechnology, Naples, Italy; Department Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
Davide Viggiano
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, via Pansini, 5 80131 Naples, Italy; Biogem, Ariano Irpino, Italy; Corresponding author
Armando Cevenini
Ceinge, Advanced Biotechnology, Naples, Italy; Department Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
Salvatore Tolone
Division of General, Mininvasive and Bariatric Surgery, University of Study of Campania “Luigi Vanvitelli”, Naples, Italy
Ludovico Docimo
Division of General, Mininvasive and Bariatric Surgery, University of Study of Campania “Luigi Vanvitelli”, Naples, Italy
Valentina Di Iorio
Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “LuigiVanvitelli”, Naples, Italy
Francesca Del Vecchio Blanco
Telethon Institute of Genetics and Medicine (TIGEM), University of Campania “Luigi Vanvitelli”, Pozzuoli, Naples, Italy
Roberta Fedele
Ceinge, Advanced Biotechnology, Naples, Italy
Francesca Simonelli
Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “LuigiVanvitelli”, Naples, Italy
Alessandra Perna
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, via Pansini, 5 80131 Naples, Italy
Vincenzo Nigro
Telethon Institute of Genetics and Medicine (TIGEM), University of Campania “Luigi Vanvitelli”, Pozzuoli, Naples, Italy
Ceinge, Advanced Biotechnology, Naples, Italy; Department Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
Miriam Zacchia
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, via Pansini, 5 80131 Naples, Italy
Summary: Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis. In vitro studies were conducted in two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3-Bbs10−/−cells) and over-expressed. The CKD status affected plasmatic metabolite fingerprinting in both patients with BBS and controls. Specific phosphatidylcholine and acylcarnitines discriminated eGFR decline only in patients with BBS. IMCD3-Bbs10−/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane and citrate synthase staining. Mass-Spectrometry-based analysis revealed that human BBS10 interacted with six mitochondrial proteins, in vitro. In conclusion, renal dysfunction correlated with abnormal phosphatidylcholine and acylcarnitines plasma levels in patients with BBS; in vitro, Bbs10 depletion caused mitochondrial defects while human BBS10 interacted with several mitochondria-related proteins, suggesting an unexplored role of this protein.
