Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q.

ABSTRACT: Pathogenic variants in SPART 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. SPART 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 Ca²⁺ versus control cells. We investigated the mitochondrial import of nuclear-encoded proteins in these fibroblasts and in another cell model carrying a SP

SUBMITTER: Diquigiovanni C 

PROVIDER: S-EPMC10335854 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature