ArticleHuman molecular genetics2022
Mouse midbrain dopaminergic neurons survive loss of the PD-associated mitochondrial protein CHCHD2.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs.Autophagy · 2026Article
- Cortical organoids reveal human-specific role of METTL5 in neurodevelopment via regulation of CHCHD2.Stem cell reports · 2026Article
- Selective vulnerability of dopaminergic neurons in Parkinson's disease connects PRKN and differential expression of CHCHD2 and GPNMB.Cell death & disease · 2026Article
- CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology.Science advances · 2025Article
- The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.Cell death & disease · 2025Article
- Clinical, neuropathological, and biochemical characterization of ALS in a large CHCHD10 R15L family.medRxiv : the preprint server for health sciences · 2025Article
- Role of the mitochondrial regulatory factor CHCHD2 in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy.The EMBO journal · 2024Article
- Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction.Molecular neurobiology · 2024Article
- High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice.EMBO molecular medicine · 2024Article
- DELE1 promotes translation-associated homeostasis, growth, and survival in mitochondrial myopathy.bioRxiv : the preprint server for biology · 2024Article
- CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly inNeural regeneration research · 2024Article
- CHCHD2 p.Thr61Ile knock-in mice exhibit motor defects and neuropathological features of Parkinson's disease.Brain pathology (Zurich, Switzerland) · 2023Article
- Neurodegeneration-associated mitochondrial proteins, CHCHD2 and CHCHD10-what distinguishes the two?Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the mitochondrial protein CHCHD2 cause autosomal dominant Parkinson's disease characterized by the preferential loss of substantia nigra dopamine (DA) neurons. Therefore, understanding the function of CHCHD2 in neurons may provide vital insights into how mitochondrial dysfunction contributes to neurodegeneration in PD. To investigate the normal requirement and function of CHCHD2 in neurons, we first examined CHCHD2 levels and showed that DA neurons have higher CHCHD2 levels than other neuron types, both in vivo and in co-culture. We then generated mice with either a targeted deletion of CHCHD2 in DA neurons or a deletion in the brain or total body. All three models were viable, and loss of CHCHD2 in the brain did not cause degeneration of DA neurons. Mice lacking CHCHD2 in DA neurons did display sex-specific changes to locomotor activity, but we did not observe differences in assays of muscle strength, exercise endurance or motor coordination. Furthermore, mitochondria derived from mice lacking CHCHD2 did not display abnormalities in OXPHOS function. Lastly, resilience to CHCHD2 deletion could not be explained by functional complementation by its paralog CHCHD10, as deletion of both CHCHD10 and CHCHD2 did not cause degeneration of DA neurons in the midbrain. These findings support the hypothesis that pathogenic CHCHD2 mutations cause PD through a toxic gain-of-function, rather than loss-of-function mechanism.
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