ArticleCell death & disease2013
Myotonic dystrophy protein kinase (DMPK) prevents ROS-induced cell death by assembling a hexokinase II-Src complex on the mitochondrial surface.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 63 citations in OpenAlex.
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- Development, opportunities, and challenges of siRNA nucleic acid drugs.Molecular therapy. Nucleic acids · 2025Review
- Muscular Dystrophies.Advances in experimental medicine and biology · 2025Review
- Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders.Cell & bioscience · 2024Review
- The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024Review
- Mitochondrial Dysfunction in Repeat Expansion Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Automatic Text-Mining Approach to Identify Molecular Target Candidates Associated with Metabolic Processes for Myotonic Dystrophy Type 1.International journal of environmental research and public health · 2023Article
- Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1.Journal of neuromuscular diseases · 2023Article
- Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart.International journal of molecular sciences · 2022Review
- Blood Transcriptome Profiling Links Immunity to Disease Severity in Myotonic Dystrophy Type 1 (DM1).International journal of molecular sciences · 2022Article
- Analysis of the Effects of Hexokinase 2 Detachment From Mitochondria-Associated Membranes with the Highly Selective Peptide HK2pep.Bio-protocol · 2021Article
- Skeletal Muscle Mitochondria Dysfunction in Genetic Neuromuscular Disorders with Cardiac Phenotype.International journal of molecular sciences · 2021Review
- Prioritization of candidate causal genes for asthma in susceptibility loci derived from UK Biobank.Communications biology · 2021Article
- Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters.International journal of molecular sciences · 2021Review
- Transcriptome profiles associated with selenium-deficiency-dependent oxidative stress identify potential diagnostic and therapeutic targets in liver cancer cells.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Hexokinase 2 displacement from mitochondria-associated membranes prompts CaEMBO reports · 2020Article
- Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation.Journal of clinical medicine · 2020Article
- Synergistic combination of DT-13 and Topotecan inhibits aerobic glycolysis in human gastric carcinoma BGC-823 cells via NM IIA/EGFR/HK II axis.Journal of cellular and molecular medicine · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biological functions of myotonic dystrophy protein kinase (DMPK), a serine/threonine kinase whose gene mutations cause myotonic dystrophy type 1 (DM1), remain poorly understood. Several DMPK isoforms exist, and the long ones (DMPK-A/B/C/D) are associated with the mitochondria, where they exert unknown activities. We have studied the isoform A of DMPK, which we have found to be prevalently associated to the outer mitochondrial membrane. The kinase activity of mitochondrial DMPK protects cells from oxidative stress and from the ensuing opening of the mitochondrial permeability transition pore (PTP), which would otherwise irreversibly commit cells to death. We observe that DMPK (i) increases the mitochondrial localization of hexokinase II (HK II), (ii) forms a multimeric complex with HK II and with the active form of the tyrosine kinase Src, binding its SH3 domain and (iii) it is tyrosine-phosphorylated by Src. Both interaction among these proteins and tyrosine phosphorylation of DMPK are increased under oxidative stress, and Src inhibition selectively enhances death in DMPK-expressing cells after HK II detachment from the mitochondria. Down-modulation of DMPK abolishes the appearance of muscle markers in in vitro myogenesis, which is rescued by oxidant scavenging. Our data indicate that, together with HK II and Src, mitochondrial DMPK is part of a multimolecular complex endowed with antioxidant and pro-survival properties that could be relevant during the function and differentiation of muscle fibers.
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