ArticleJournal of molecular and cellular cardiology2019
Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.
Article in Journal of molecular and cellular cardiology, 2019. 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, 72 citations in OpenAlex.
- Molecular mechanisms underlying FCCP-induced mitophagy in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Targeting Mitochondria for Postoperative Cognitive Dysfunction: From Mechanisms to Therapeutics.Molecular neurobiology · 2026Review
- Identification of biomarkers associated with mitochondria and macrophage polarization in acute myocardial infarction: a bioinformatics analysis and validation study.Journal of cardiothoracic surgery · 2026Article
- FIS1 dependent peripheral fission exacerbates mitochondrial fragmentation and dysfunction in prion diseases.Frontiers in neuroscience · 2026Article
- Failure of lysosomal acidification and endomembrane network in neurodegeneration.Experimental & molecular medicine · 2025Review
- Methylene Blue Attenuates 3-Nitropropionic Acid-Induced Oxidative Stress and Mitochondrial Dysfunction in Striatal Cells: Therapeutic Implications in Huntington's Disease Neuropathology.International journal of molecular sciences · 2025Article
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- Mitophagy's impacts on cancer and neurodegenerative diseases: implications for future therapies.Journal of hematology & oncology · 2025Review
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Fis1 regulates mitochondrial morphology, bioenergetics and removal of mitochondrial DNA damage in irradiated glioblastoma cells.Journal of cell science · 2025Article
- The therapeutic potential of (R)-carvedilol in Huntington's disease through enhancement of autophagy-lysosomal pathway via GSK-3β inhibition.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.Biomedicines · 2025Review
- Multi-target-directed therapeutic strategies for Alzheimer's disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition.Chemical science · 2025Review
- Targeting mitochondrial quality control: new therapeutic strategies for major diseases.Military Medical Research · 2024Review
- Review
- Enhanced presynaptic mitochondrial energy production is required for memory formation.Scientific reports · 2023Article
- Targeting an allosteric site in dynamin-related protein 1 to inhibit Fis1-mediated mitochondrial dysfunction.Nature communications · 2023Article
- CLUH functions as a negative regulator of inflammation in human macrophages and determines ulcerative colitis pathogenesis.JCI insight · 2023Article
- Mitochondrial Fission as a Therapeutic Target for Metabolic Diseases: Insights into Antioxidant Strategies.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.
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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 Socratic graph.