ArticlePLoS genetics2012
The mitochondrial chaperone protein TRAP1 mitigates α-Synuclein toxicity.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 140 citations in OpenAlex.
- SIRT5-mediated HSDL2 desuccinylation promotes diabetic-associated cognitive dysfunction via disrupting mitochondrial TRAP1.Cell biology and toxicology · 2026Article
- Systematic evaluation of mitochondrial morphology regulators for amelioration of neuronal α-synucleinopathy.NPJ Parkinson's disease · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinson's disease.Protein science : a publication of the Protein Society · 2025Article
- The novel amino-artemisinin derivative WHN-11 disrupts mitochondria and protein homeostasis, and induces autophagy and apoptosis in cancer cells.Scientific reports · 2025Article
- Patient-centered brain transcriptomic and multimodal imaging determinants of clinical progression, physical activity, and treatment needs in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Article
- Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.Research square · 2024Article
- The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson's Disease Pathogenesis.Nutrients · 2023Review
- α-Synuclein and biological membranes: the danger of loving too much.Chemical communications (Cambridge, England) · 2023Review
- PINK1-Dependent Mitophagy Inhibits Elevated Ubiquitin Phosphorylation Caused by Mitochondrial Damage.Journal of medicinal chemistry · 2023Article
- Asymmetric Presynaptic Depletion of Dopamine Neurons in aInternational journal of molecular sciences · 2023Article
- TRAP1 Is Expressed in Human Retinal Pigment Epithelial Cells and Is Required to Maintain their Energetic Status.Antioxidants (Basel, Switzerland) · 2023Article
- Analysis of α-syn andFrontiers in cellular neuroscience · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Exploring the Role of Ubiquitin-Proteasome System in Parkinson's Disease.Molecular neurobiology · 2022Review
- The Mitochondrial HSP90 Paralog TRAP1: Structural Dynamics, Interactome, Role in Metabolic Regulation, and Inhibitors.Biomolecules · 2022Review
- Enhanced Expression of TRAP1 Protects Mitochondrial Function in Motor Neurons under Conditions of Oxidative Stress.International journal of molecular sciences · 2022Article
- The relationship of alpha-synuclein to mitochondrial dynamics and quality control.Frontiers in molecular neuroscience · 2022Review
- TRAP1 in Oxidative Stress and Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]α-Synuclein-induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]α-Synuclein expression. In addition, decreased TRAP1 expression in [A53T]α-Synuclein-expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T]α-Synuclein-induced sensitivity to rotenone treatment. In human (non)neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T]α-Synuclein-induced sensitivity to oxidative stress treatment. [A53T]α-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T]α-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T]α-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to α-Synuclein.
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