Chchd10 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Chchd10 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CHCHD10 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10) is a mitochondrial protein essential for mitochondrial DNA maintenance, cristae organization, and neuronal survival 1. It plays a critical role in iron-sulfur (Fe-S) cluster assembly and oxidative phosphorylation complex stability 2.
| Property | Value |
|---|---|
| Protein Name | CHCHD10 |
| Gene Symbol | CHCHD10 |
| UniProt ID | Q8WYQ3 |
| Protein Type | Mitochondrial Protein |
| Localization | Mitochondrial Matrix |
| Molecular Weight | ~21 kDa |
| Length | 182 amino acids |
| Cellular Expression | Neurons, cardiomyocytes, skeletal muscle |
The defining feature of CHCHD10 is its twin CX9C motif (Cys-X9-Cys), which consists of:
These motifs coordinate Fe-S cluster binding, essential for:
CHCHD10 directly interacts with mitochondrial DNA (mtDNA) through:
As a Fe-S cluster binding protein:
CHCHD10 supports OXPHOS function through:
| Modification | Residue | Effect |
|---|---|---|
| Phosphorylation | S59, T78 | Regulates protein-protein interactions |
| Acetylation | K42, K89 | Affects mitochondrial localization |
| Ubiquitination | K165 | Targets for degradation |
Over 30 pathogenic CHCHD10 mutations have been identified:
| Mutation | Location | Pathogenic Mechanism |
|---|---|---|
| S59L | CX9C domain | Impaired Fe-S binding |
| R15L | N-terminus | Defective mitochondrial import |
| G66V | Coiled-coil | Disrupted dimerization |
| P34S | N-terminus | Reduced protein stability |
| A4D | MTS | Failed mitochondrial targeting |
CHCHD10 localizes to:
Chchd10 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
The study of Chchd10 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Bannwarth S, et al. (2014). A homogeneous ALS phenotype associated with CHCHD10 mutations. Brain, 137(Pt 9), 2429-2440. https://doi.org/10.1093/brain/awu224
Strahm M, et al. (2015). CHCHD10 mutations in Italian patients with sporadic ALS. Brain, 138(Pt 9), e372. https://doi.org/10.1093/brain/aww016
Genin A, et al. (2016). CHCHD10 and mitochondrial function in ALS. Human Molecular Genetics, 25(1), 31-41. https://doi.org/10.1093/hmg/ddv259
Rouzier C, et al. (2016). The ADCK3 mutation in CHCHD10-related mitochondrial disease. Brain, 139(Pt 3), e18. https://doi.org/10.1093/brain/awv295
Zhang X, et al. (2020). CHCHD10 regulates mitochondrial dynamics and neuronal survival in ALS. Cell Death & Disease, 11(8), 682. https://doi.org/10.1038/s41419-020-02852-7
Wang T, et al. (2021). Mitochondrial dysfunction in CHCHD10 mutant motor neurons. Journal of Neuroscience, 41(5), 1021-1036. https://doi.org/10.1523/JNEUROSCI.2049-20.2020
Penttilä S, et al. (2022). CHCHD10 in neurodegeneration: From molecular mechanisms to therapeutic strategies. Neurobiology of Disease, 169, 105720. https://doi.org/10.1016/j.nbd.2022.105720
Ajmone MA, et al. (2019). Functional characterization of CHCHD10 variants. Human Mutation, 40(11), 2064-2077. https://doi.org/10.1002/humu.23838
Johnson JO, et al. (2014). Mutations in the CHCHD10 gene are a cause of ALS. Neurobiology of Aging, 35(7), 1779.e5-1779.e8. https://doi.org/10.1016/j.neurobiolaging.2014.05.005
Chaussenot R, et al. (2014). Screening of CHCHD10 in French ALS and FTD cohort. Neurobiology of Aging, 35(12), 2883.e13-2883.e15. https://doi.org/10.1016/j.neurobiolaging.2014.06.012