ArticleNature communications2025
Dysregulation of mitochondrial α-ketoglutarate dehydrogenase leads to elevated lipid peroxidation in CHCHD2-linked Parkinson's disease models.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Cortical organoids reveal human-specific role of METTL5 in neurodevelopment via regulation of CHCHD2.Stem cell reports · 2026Article
- Direct quantification of the metabolic heat output of individual Drosophila brains.Cell reports methods · 2026Article
- The Role of Gut Microbiota in the Association between Air Pollution and Cognitive Function in Older Adults.Environmental health perspectives · 2026Article
- Parkinson's disease: pathogenesis and therapeutic strategies.Molecular biomedicine · 2026Review
- Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.Signal transduction and targeted therapy · 2026Article
- Decoding the Metabolic Signatures of Neurodegeneration Diseases: Advances in Mass Spectrometry-Based Metabolomics.Metabolites · 2026Review
- Ferroptosis-autophagy crosstalk in bladder cancer: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Glycerol 3-phosphate acyltransferase exacerbates α-synuclein-induced toxicity by increasing lipid peroxidation.Nature communications · 2026Article
- Development and external validation of a machine learning-based model for identifying advanced Parkinson's disease.Frontiers in aging neuroscience · 2026Article
- Potential role of theFrontiers in genetics · 2026Article
- Neuromodulatory control of energy reserves in dopaminergic neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Dysregulation of mitochondrial function has been implicated in Parkinson's disease (PD), but the role of mitochondrial metabolism in disease pathogenesis remains to be elucidated. Using an unbiased metabolomic analysis of purified mitochondria, we identified alterations in α-ketoglutarate dehydrogenase (KGDH) pathway upon loss of PD-linked CHCHD2 protein. KGDH, a rate-limiting enzyme complex in the tricarboxylic acid cycle, was decreased in CHCHD2-deficient male mouse brains and human dopaminergic neurons. This deficiency of KGDH led to elevated α-ketoglutarate and increased lipid peroxidation. Treatment of CHCHD2-deficient dopaminergic neurons with lipoic acid, a KGDH cofactor and antioxidant agent, resulted in decreased levels of lipid peroxidation and phosphorylated α-synuclein. CHCHD10, a close homolog of CHCHD2 that is primarily linked to amyotrophic lateral sclerosis/frontotemporal dementia, did not affect the KGDH pathway or lipid peroxidation. Together, these results identify KGDH metabolic pathway as a targetable mitochondrial mechanism for correction of increased lipid peroxidation and α-synuclein in Parkinson's disease.
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