ArticleAmerican journal of human genetics2018
Mutations in PMPCB Encoding the Catalytic Subunit of the Mitochondrial Presequence Protease Cause Neurodegeneration in Early Childhood.
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 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- Platelet-derived microparticles induce CD8Experimental & molecular medicine · 2026Article
- HUNTER catches N-terminal prey of ICP55 in the mitochondria.Nature structural & molecular biology · 2026Article
- A single-amino-acid cleavage controls global mitochondrial complex integrity.Nature structural & molecular biology · 2026Article
- Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.EMBO molecular medicine · 2026Article
- The long road to diagnosis: recessive PMPCB deficiency hidden behind a dominant familial VCP defect.Molecular genetics and metabolism reports · 2026Article
- Proteolytic control of mitochondrial protein translocases.Protein science : a publication of the Protein Society · 2026Review
- Pmpcb modulates zebrafish neurogenesis and stress resistance via regulating mitochondria metabolism and function.Molecular neurobiology · 2026Article
- Clinical and genetic analysis of multiple mitochondrial dysfunctions syndrome type 6 caused by biallelicFrontiers in pediatrics · 2026Article
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- The phenomenon of anhydrobiosis-structural and functional changes in yeast cells.Applied microbiology and biotechnology · 2025Review
- OXA1L deficiency causes mitochondrial myopathy via reactive oxygen species regulated nuclear factor kappa B signalling pathway.Clinical and translational medicine · 2025Article
- Human mitochondrial peroxiredoxin Prdx3 is dually localized in the intermembrane space and matrix subcompartments.Redox biology · 2024Article
- Defects in the Maturation of Mitochondrial Iron-Sulfur Proteins: Biophysical Investigation of the MMDS3 Causing Gly104Cys Variant of IBA57.International journal of molecular sciences · 2024Article
- A Multi-Dimensional Approach to Map Disease Relationships Challenges Classical Disease Views.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Leigh syndrome with developmental regression and ataxia due to a novel splicing variant in the PMPCB gene.Journal of human genetics · 2024Article
- Article
- Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- A tale of two pathways: Regulation of proteostasis by UPRCurrent opinion in neurobiology · 2023Review
Corrections and comments
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Authors and funding
28 authors at 13 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial disorders causing neurodegeneration in childhood are genetically heterogeneous, and the underlying genetic etiology remains unknown in many affected individuals. We identified biallelic variants in PMPCB in individuals of four families including one family with two affected siblings with neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins. Mitochondria isolated from two fibroblast cell lines and induced pluripotent stem cells derived from one affected individual and differentiated neuroepithelial stem cells showed reduced PMPCB levels and accumulation of the processing intermediate of frataxin, a sensitive substrate for MPP dysfunction. Introduction of the identified PMPCB variants into the homologous S. cerevisiae Mas1 protein resulted in a severe growth and MPP processing defect leading to the accumulation of mitochondrial precursor proteins and early impairment of the biogenesis of iron-sulfur clusters, which are indispensable for a broad range of crucial cellular functions. Analysis of biopsy materials of an affected individual revealed changes and decreased activity in iron-sulfur cluster-containing respiratory chain complexes and dysfunction of mitochondrial and cytosolic Fe-S cluster-dependent enzymes. We conclude that biallelic mutations in PMPCB cause defects in MPP proteolytic activity leading to dysregulation of iron-sulfur cluster biogenesis and triggering a complex neurological phenotype of neurodegeneration in early childhood.
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