{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Diquigiovanni C"],"funding":["Telethon","PNNR","Fondazione Umberto Veronesi"],"pagination":["230040"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10335854"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(7)"],"pubmed_abstract":["Pathogenic variants in <i>SPART</i> cause Troyer syndrome, characterized by lower extremity spasticity and weakness, short stature and cognitive impairment, and a severe mitochondrial impairment. Herein, we report the identification of a role of Spartin in nuclear-encoded mitochondrial proteins. <i>SPART</i> biallelic missense variants were detected in a 5-year-old boy with short stature, developmental delay and muscle weakness with impaired walking distance. Patient-derived fibroblasts showed an altered mitochondrial network, decreased mitochondrial respiration, increased mitochondrial reactive oxygen species and altered Ca<sup>2+</sup> versus control cells. We investigated the mitochondrial import of nuclear-encoded proteins in these fibroblasts and in another cell model carrying a <i>SPART</i> loss-of-function mutation. In both cell models the mitochondrial import was impaired, leading to a significant decrease in different proteins, including two key enzymes involved in CoQ10 (CoQ) synthesis, COQ7 and COQ9, with a severe reduction in CoQ content, versus control cells. CoQ supplementation restored cellular ATP levels to the same extent shown by the re-expression of wild-type SPART, suggesting CoQ treatment as a promising therapeutic approach for patients carrying mutations in <i>SPART</i>."],"journal":["Open biology"],"pubmed_title":["Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q."],"pmcid":["PMC10335854"],"funding_grant_id":["CN00000041","GGP15171"],"pubmed_authors":["Rizzardi N","Braun F","De Nicolo B","Haack TB","Bonora E","Severi G","Fato R","Bertrand M","Diquigiovanni C","Seri M","Marina AD","Cuna E","Kampmeier A","Liparulo I","Bianco F","Cataldi-Stagetti E","Bergamini C","Kuechler A"],"additional_accession":[]},"is_claimable":false,"name":"Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q.","description":"Pathogenic variants in <i>SPART</i> cause Troyer syndrome, characterized by lower extremity spasticity and weakness, short stature and cognitive impairment, and a severe mitochondrial impairment. Herein, we report the identification of a role of Spartin in nuclear-encoded mitochondrial proteins. <i>SPART</i> biallelic missense variants were detected in a 5-year-old boy with short stature, developmental delay and muscle weakness with impaired walking distance. Patient-derived fibroblasts showed an altered mitochondrial network, decreased mitochondrial respiration, increased mitochondrial reactive oxygen species and altered Ca<sup>2+</sup> versus control cells. We investigated the mitochondrial import of nuclear-encoded proteins in these fibroblasts and in another cell model carrying a <i>SPART</i> loss-of-function mutation. In both cell models the mitochondrial import was impaired, leading to a significant decrease in different proteins, including two key enzymes involved in CoQ10 (CoQ) synthesis, COQ7 and COQ9, with a severe reduction in CoQ content, versus control cells. CoQ supplementation restored cellular ATP levels to the same extent shown by the re-expression of wild-type SPART, suggesting CoQ treatment as a promising therapeutic approach for patients carrying mutations in <i>SPART</i>.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jul","modification":"2024-11-13T09:06:26.95Z","creation":"2024-11-13T09:06:26.95Z"},"accession":"S-EPMC10335854","cross_references":{"pubmed":["37433330"],"doi":["10.1098/rsob.230040"]}}