ArticleJournal of molecular medicine (Berlin, Germany)2011
Successful TAT-mediated enzyme replacement therapy in a mouse model of mitochondrial E3 deficiency.
Article in Journal of molecular medicine (Berlin, Germany), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- Rescue of the First Mitochondrial Membrane Carrier, the mPiC, by TAT-Mediated Protein Replacement Treatment.International journal of molecular sciences · 2025Article
- dldhcri3 zebrafish exhibit altered mitochondrial ultrastructure, morphology, and dysfunction partially rescued by probucol or thiamine.JCI insight · 2024Article
- Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of the structural and functional characterization of LADH and its pathogenic variants.Biologia futura · 2023Review
- Review
- Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs.Molecules (Basel, Switzerland) · 2022Review
- Cell penetrating peptide: A potent delivery system in vaccine development.Frontiers in pharmacology · 2022Review
- 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
- TAT-Conjugated NDUFS8 Can Be Transduced into Mitochondria in a Membrane-Potential-Independent Manner and Rescue Complex I Deficiency.International journal of molecular sciences · 2021Article
- Article
- An Updated View on the Molecular Pathomechanisms of Human Dihydrolipoamide Dehydrogenase Deficiency in Light of Novel Crystallographic Evidence.Neurochemical research · 2019Review
- Cell and Gene Therapies for Mucopolysaccharidoses: Base Editing and Therapeutic Delivery to the CNS.Diseases (Basel, Switzerland) · 2019Review
- Import of TAT-Conjugated Propionyl Coenzyme A Carboxylase Using Models of Propionic Acidemia.Molecular and cellular biology · 2018Article
- TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells.Journal of cellular and molecular medicine · 2018Article
- Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron.PloS one · 2017Article
- Towards the development of an enzyme replacement therapy for the metabolic disorder propionic acidemia.Molecular genetics and metabolism reports · 2016Article
- Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease.International journal of molecular sciences · 2016Review
- Cell-permeable protein therapy for complex I dysfunction.Journal of bioenergetics and biomembranes · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medicine today offers no cure for patients suffering from mitochondrial disorders, such as lipoamide dehydrogenase (LAD; also known as E3) deficiency, and treatment is limited to symptomatic care. LAD is one of the components of the α-ketoacid dehydrogenase complexes, which are mitochondrial multienzyme complexes crucial for the metabolism of carbohydrates and amino acids. Recently, we tested the therapeutic approach for treating mitochondrial disorders whereby the activity of multicomponent complexes in the mitochondria is restored by TAT-mediated enzyme replacement therapy (ERT). The LAD deficiency disease was used before as a proof-of-principle in vitro, in patients' cells, utilizing the TAT-LAD fusion protein. In this report, we present successful TAT-mediated ERT in an in vivo mouse model using E3-deficient mice. We demonstrate the delivery of TAT-LAD into E3-deficient mice tissues and that a single administration of TAT-LAD results in a significant increase in the enzymatic activity of the mitochondrial multienzyme complex pyruvate dehydrogenase complex within the liver, heart and, most importantly, the brain of TAT-LAD-treated E3-deficient mice. We believe that this TAT-mediated ERT approach could change the management of mitochondrial disorders and of other metabolic diseases in modern medicine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.