ArticleMolecular medicine (Cambridge, Mass.)2013
Replacement of the C6ORF66 assembly factor (NDUFAF4) restores complex I activity in patient cells.
Article in Molecular medicine (Cambridge, Mass.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- A cell-permeable nanobody to restore F508del cystic fibrosis transmembrane conductance regulator activity.Nature chemical biology · 2026Article
- Rescue of the First Mitochondrial Membrane Carrier, the mPiC, by TAT-Mediated Protein Replacement Treatment.International journal of molecular sciences · 2025Article
- Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population.American journal of physiology. Heart and circulatory physiology · 2024Article
- Review
- Genome-wide association and selective sweep analyses reveal genetic loci for FCR of egg production traits in ducks.Genetics, selection, evolution : GSE · 2021Article
- Genetic and Covalent Protein Modification Strategies to Facilitate Intracellular Delivery.Biomacromolecules · 2021Review
- TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases.Life (Basel, Switzerland) · 2021Review
- Import of TAT-Conjugated Propionyl Coenzyme A Carboxylase Using Models of Propionic Acidemia.Molecular and cellular biology · 2018Article
- NDUFAF4 variants are associated with Leigh syndrome and cause a specific mitochondrial complex I assembly defect.European journal of human genetics : EJHG · 2017Article
- Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem.Biomolecular concepts · 2017Review
- Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease.International journal of molecular sciences · 2016Review
- Global profiling of co- and post-translationally N-myristoylated proteomes in human cells.Nature communications · 2014Article
- Cell-permeable protein therapy for complex I dysfunction.Journal of bioenergetics and biomembranes · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disorders of the oxidative phosphorylation (OXPHOS) system frequently result in a severe multisystem disease with the consequence of early childhood death. Among these disorders, isolated complex I deficiency is the most frequently diagnosed, accounting for one-third of all cases of respiratory chain deficiency. We chose to focus on complex I deficiency, caused by mutation in the assembly factor chromosome 6, open reading frame 66 (C6ORF66; NADH dehydrogenase [ubiquinone] complex I assembly factor 4 [NDUFAF4]) protein. We used the approach of cell- and organelle-directed protein/enzyme replacement therapy, with the transactivator of transcription (TAT) peptide as the moiety delivery system. This step will enable us to deliver the wild-type assembly factor C6ORF66 into patient cells and their mitochondria, leading to the proper assembly and function of complex I and, as a result, to a functional OXPHOS system. We designed and constructed the TAT-ORF fusion protein by gene fusion techniques, expressed the protein in an Escherichia coli expression system and highly purified it. Our results indicate that TAT-ORF enters patients' cells and their mitochondria rapidly and efficiently. TAT-ORF is biologically active and led to an increase in complex I activity. TAT-ORF also increased the number of patient cells and improved the activity of their mitochondria. Moreover, we observed an increase in ATP production, a decrease in the content of mitochondria and a decrease in the level of reactive oxygen species. Our results suggest that this approach of protein replacement therapy for the treatment of mitochondrial disorders is a promising one.
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