{{> infobox .infobox-protein
| name = CHCHD5 Protein
| gene = CHCHD5
| uniprot = Q96EW6
| pdb = 2M9M
| molecular_weight = ~22 kDa
| localization = Mitochondria, Inner membrane
| family = CHCH domain family
}}
{{> infobox is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
CHCHD5 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 5) is a small mitochondrial protein (~180 amino acids) containing two conserved CHCH domains. Each CHCH domain features two cysteine residues that form a disulfide bond, creating a compact helical structure that targets the protein to the mitochondrial inner membrane. The protein lacks a canonical N-terminal mitochondrial targeting sequence but uses its hydrophobic CHCH domains for membrane insertion.
In neurons, CHCHD5 is primarily localized to the mitochondrial cristae, where it plays a role in:
[1] CHCHD5 has been implicated in Alzheimer's disease through mitochondrial dysfunction. Studies show reduced CHCHD5 expression in AD brains, which correlates with:
In PD models, CHCHD5 alterations contribute to:
[3] CHCHD5 dysregulation has been observed in ALS, particularly in mitochondrial fractions, suggesting a role in motor neuron mitochondrial homeostasis.
Currently, no direct CHCHD5-targeted therapeutics exist. Therapeutic strategies focus on: