RMND1 dysfunction causes OXPHOS deficiency and alters mitoribosomal protein homeostasis in vivo

ABSTRACT: Pathogenic, bi-allelic variants in RMND1 typically manifest as an early-onset multisystemic mitochondrial disease, yet the consequences of RMND1 dysfunction in vivo remain poorly understood. To answer this question, we generated and characterized the first in vivo model of RMND1-related disease, carrying the recurrent p.Asn238Ser variant. Homozygous Rmnd1N238S mice exhibit growth defect, premature mortality, and a multisystem phenotype marked by widespread tissue-dependent defects in oxidative phosphorylation assembly and activity. Quantitative proteomic analysis of Rmnd1N238S heart revealed extensive metabolic remodeling, with significant alterations in the abundance of mitoribosomal proteins and factors associated with mitoribosome maturation. Selected changes in mitoribosomal protein ab

SUBMITTER: Alba Pesini 

PROVIDER: S-SCDT-10_1038-S44321-026-00534-1 | biostudies-other |

REPOSITORIES: biostudies-other