ArticleAmerican journal of human genetics2018
Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
- Fructose directly remodels the translocase of the outer membrane to impair oxidative phosphorylation in podocytes.Signal transduction and targeted therapy · 2026Article
- Antenatal Presentation of MRPS22-Related Mitochondrial Disease Confirmed With Rapid Proteomics.JIMD reports · 2026Article
- A biallelic MRPL42 variant causes a combined oxidative phosphorylation deficiency syndrome revealed by multi-omics.NPJ genomic medicine · 2026Article
- Bioenergetic Signatures of DLD Deficiency: Dissecting PDHc- and α-KGDHc-Linked Defects.Antioxidants (Basel, Switzerland) · 2025Article
- Immunogenomic diversity of triple-negative breast cancers in obese and non-obese black and white women.NPJ breast cancer · 2025Article
- Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish.European journal of human genetics : EJHG · 2025Article
- The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss.Molecular neurobiology · 2025Review
- Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome.Annals of clinical and translational neurology · 2025Article
- Bi-allelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered apoptosis and a Perrault-syndrome-spectrum phenotype.American journal of human genetics · 2025Article
- Targeted next-generation sequencing of candidate regions identified by GWAS revealed SNPs associated with IBD in GSDs.Frontiers in veterinary science · 2025Article
- Analysis of Complexome Profiles with the Gaussian Interaction Profiler (GIP) Reveals Novel Protein Complexes inJournal of proteome research · 2024Article
- Maternal Undernutrition Affects Fetal Thymus DNA Methylation, Gene Expression, and, Thereby, Metabolism and Immunopoiesis in Wagyu (Japanese Black) Cattle.International journal of molecular sciences · 2024Article
- Biallelic variants inmedRxiv : the preprint server for health sciences · 2024Article
- Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation.iScience · 2024Article
- Protein assemblies in theFrontiers in plant science · 2024Article
- Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.Frontiers in cell and developmental biology · 2024Review
- Translation Fidelity and Respiration Deficits in CLPP-Deficient Tissues: Mechanistic Insights from Mitochondrial Complexome Profiling.International journal of molecular sciences · 2023Article
- Genetic, metabolic and clinical delineation of an MRPS23-associated mitochondrial disorder.Scientific reports · 2023Article
- Let's make it clear: systematic exploration of mitochondrial DNA- and RNA-protein complexes by complexome profiling.Nucleic acids research · 2023Article
- Comparative Clustering (CompaCt) of eukaryote complexomes identifies novel interactions and sheds light on protein complex evolution.PLoS computational biology · 2023Article
Corrections and comments
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Authors and funding
28 authors at 13 institutions in 4 countries.
Funding
Abstract
Biogenesis of the mitochondrial oxidative phosphorylation system, which produces the bulk of ATP for almost all eukaryotic cells, depends on the translation of 13 mtDNA-encoded polypeptides by mitochondria-specific ribosomes in the mitochondrial matrix. These mitoribosomes are dual-origin ribonucleoprotein complexes, which contain mtDNA-encoded rRNAs and tRNAs and ∼80 nucleus-encoded proteins. An increasing number of gene mutations that impair mitoribosomal function and result in multiple OXPHOS deficiencies are being linked to human mitochondrial diseases. Using exome sequencing in two unrelated subjects presenting with sensorineural hearing impairment, mild developmental delay, hypoglycemia, and a combined OXPHOS deficiency, we identified mutations in the gene encoding the mitochondrial ribosomal protein S2, which has not previously been implicated in disease. Characterization of subjects' fibroblasts revealed a decrease in the steady-state amounts of mutant MRPS2, and this decrease was shown by complexome profiling to prevent the assembly of the small mitoribosomal subunit. In turn, mitochondrial translation was inhibited, resulting in a combined OXPHOS deficiency detectable in subjects' muscle and liver biopsies as well as in cultured skin fibroblasts. Reintroduction of wild-type MRPS2 restored mitochondrial translation and OXPHOS assembly. The combination of lactic acidemia, hypoglycemia, and sensorineural hearing loss, especially in the presence of a combined OXPHOS deficiency, should raise suspicion for a ribosomal-subunit-related mitochondrial defect, and clinical recognition could allow for a targeted diagnostic approach. The identification of MRPS2 as an additional gene related to mitochondrial disease further expands the genetic and phenotypic spectra of OXPHOS deficiencies caused by impaired mitochondrial translation.
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