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

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 epith...

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Veröffentlicht in:iScience 2022-11, Vol.25 (11), p.105230-105230, Article 105230
Hauptverfasser: Marchese, Emanuela, Caterino, Marianna, Viggiano, Davide, Cevenini, Armando, Tolone, Salvatore, Docimo, Ludovico, Di Iorio, Valentina, Del Vecchio Blanco, Francesca, Fedele, Roberta, Simonelli, Francesca, Perna, Alessandra, Nigro, Vincenzo, Capasso, Giovambattista, Ruoppolo, Margherita, Zacchia, Miriam
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Targeted Metabolomics reveals a unique serum fingerprinting of patients with BBS with CKD•Acylcarnitines are among the most significant alterations•In renal epithelial cells, Bbs10 depletion leads to mitochondrial abnormalities•Human BBS 10 interacts with six mitochondria-related proteins Pathophysiology; Metabolomics
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.105230