Metabolomic fingerprinting of renal disease progression in Bardet-Biedl syndrome reveals mitochondrial dysfunction in kidney tubular cells

• DOI: 10.1016/j.isci.2022.105230
• Publication Date: 2022-09-27T10:43:43Z
• Authors: Emanuela Marchese; Marianna Caterino; Davide Viggiano; Armando Cevenini; Salvatore Tolone; Ludovico Docimo; Valentina Di Iorio; Francesca Del Vec...; Roberta Fedele; Francesca Simonelli; Alessandra Perna; Vincenzo Nigro; Giovambattista Ca...; Margherita Ruoppolo; Miriam Zacchia
• Keywords: Bardet–Biedl Syndrome

Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine BBS and 30 controls underwent serum-targeted metabolomic analysis. In vitro studies were conducted two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3-Bbs10-/-cells) over-expressed. The CKD status affected plasmatic metabolite fingerprinting both controls. Specific phosphatidylcholine acylcarnitines discriminated eGFR decline only BBS. IMCD3-Bbs10-/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane citrate synthase staining. Mass-Spectrometry-based analysis revealed that human interacted six proteins, vitro. conclusion, renal dysfunction correlated abnormal plasma levels BBS; vitro, depletion caused defects while several mitochondria-related suggesting an unexplored role this protein.