CHCHD10 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10) is a mitochondrial protein encoded by the CHCHD10 gene, initially identified as a stability factor for mitochondrial DNA (mtDNA) and later implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease. First described in 2010, CHCHD10 has emerged as a critical regulator of mitochondrial cristae structure, respiratory chain function, and neuronal survival [1].
The discovery of disease-causing mutations in CHCHD10 in 2015 linked it to a spectrum of neurodegenerative disorders, highlighting the importance of mitochondrial integrity in neuronal health. CHCHD10 localizes to the mitochondrial intermembrane space, where it interacts with other mitochondrial proteins to maintain cristae architecture and mtDNA nucleoid organization.
| CHCHD10 | |
|---|---|
| Full Name | Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10 |
| Gene | CHCHD10 |
| UniProt ID | [Q8N4L2](https://www.uniprot.org/uniprot/Q8N4L2) |
| Protein Size | 146 amino acids |
| Protein Family | CHCH domain-containing protein family |
| Chromosomal Location | 22q11.23 |
| Subcellular Location | Mitochondrial intermembrane space |
| Associated Disease | ALS, FTD, PD, SMA with myoclonic epilepsy |
CHCHD10 contains characteristic structural features:
CHCHD10 plays a critical role in mtDNA stability:
CHCHD10 is essential for mitochondrial cristae organization:
Multiple pathogenic variants have been identified in CHCHD10:
| Mutation | Effect | Disease | Reference |
|---|---|---|---|
| p.Gly170Val | Missense, toxic | ALS/FTD | [6] |
| p.Arg102Leu | Missense, loss of function | SMA/ALS | [7] |
| p.Ser149Leu | Missense, toxic | ALS/FTD | [8] |
| p.Arg15His | Missense, toxic | FTD | [6:1] |
CHCHD10 mutations cause disease through multiple mechanisms:
CHCHD10 has been implicated in PD pathogenesis:
CHCHD10 interacts with several key mitochondrial proteins:
Wenzel L, et al. "CHCHD10 gene structure and expression." Gene. 2010. ↩︎
Martinho M, et al. "CHCHD10 mutations cause mitochondrial dysfunction." EMBO J. 2015. ↩︎
Wang S, et al. "CHCHD10 and OXPHOS complex assembly." Biochim Biophys Acta. 2022. ↩︎
Liu Y, et al. "CHCHD10 regulates mitochondrial calcium handling." Cell Calcium. 2022. ↩︎
Morris M, et al. "CHCHD10 in synaptic mitochondria function." J Neurosci Res. 2023. ↩︎
Bannerman C, et al. "CHCHD10 linked to ALS and FTD." Nat Neurosci. 2015. ↩︎ ↩︎
Zhang M, et al. "CHCHD10 mutation in spinal muscular atrophy with myoclonic epilepsy." Neurology. 2015. ↩︎
Yang L, et al. "CHCHD10 mutations in ALS/FTD families." Brain. 2021. ↩︎
Gautier CA, et al. "CHCHD10 aggregates in ALS/FTD neurons." Acta Neuropathol. 2016. ↩︎
Zhou H, et al. "CRISPR-based therapy for CHCHD10 mutations." Nat Commun. 2024. ↩︎
Yang F, et al. "CHCHD10 genetic variants and PD risk." J Neurol Neurosurg Psychiatry. 2023. ↩︎
Chen Z, et al. "CHCHD10 and PINK1 interaction in mitophagy." Autophagy. 2021. ↩︎