ArticleEMBO molecular medicine2015
Impaired GAPDH-induced mitophagy contributes to the pathology of Huntington's disease.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.Translational neurodegeneration · 2026Review
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Review
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence-Associated Pathologies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Direct targets of MEF2C are enriched for genes associated with schizophrenia and cognitive function and are involved in neuron development and mitochondrial function.PLoS genetics · 2024Article
- Huntington's disease affects mitochondrial network dynamics predisposing to pathogenic mitochondrial DNA mutations.Brain : a journal of neurology · 2024Article
- Exploring the neuroprotective role of artesunate in mouse models of anti-NMDAR encephalitis: insights from molecular mechanisms and transmission electron microscopy.Cell communication and signaling : CCS · 2024Article
- Identification of mitophagy-associated proteins profile as potential plasma biomarkers of idiopathic Parkinson's disease.CNS neuroscience & therapeutics · 2024Article
- Lowering mutant huntingtin by small molecules relieves Huntington's disease symptoms and progression.EMBO molecular medicine · 2024Article
- Review
- Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Mechanism of Nardostachyos Radix et Rhizoma-Salidroside in the treatment of premature ventricular beats based on network pharmacology and molecular docking.Scientific reports · 2023Article
- Review
- Huntingtin Interacting Proteins and Pathological Implications.International journal of molecular sciences · 2023Review
- Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired.Nature communications · 2023Article
- The mitophagy pathway and its implications in human diseases.Signal transduction and targeted therapy · 2023Review
- A perspective on autophagy and transcription factor EB in Alcohol-Associated Alzheimer's disease.Biochemical pharmacology · 2023Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
Mitochondrial dysfunction is implicated in multiple neurodegenerative diseases. In order to maintain a healthy population of functional mitochondria in cells, defective mitochondria must be properly eliminated by lysosomal machinery in a process referred to as mitophagy. Here, we uncover a new molecular mechanism underlying mitophagy driven by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) under the pathological condition of Huntington's disease (HD) caused by expansion of polyglutamine repeats. Expression of expanded polyglutamine tracts catalytically inactivates GAPDH (iGAPDH), which triggers its selective association with damaged mitochondria in several cell culture models of HD. Through this mechanism, iGAPDH serves as a signaling molecule to induce direct engulfment of damaged mitochondria into lysosomes (micro-mitophagy). However, abnormal interaction of mitochondrial GAPDH with long polyglutamine tracts stalled GAPDH-mediated mitophagy, leading to accumulation of damaged mitochondria, and increased cell death. We further demonstrated that overexpression of inactive GAPDH rescues this blunted process and enhances mitochondrial function and cell survival, indicating a role for GAPDH-driven mitophagy in the pathology of HD.
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