CHCHD10
CHCHD10, also known as Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10, is a human gene that encodes a protein localized to the mitochondrial intermembrane space. This protein plays a crucial role in mitochondrial structure, function, and dynamics, including mitochondrial cristae morphology, respiratory chain function, and mitochondrial genome maintenance.
Mutations in the CHCHD10 gene are associated with a range of neurological disorders, including:
-
Frontotemporal lobar degeneration (FTLD): A neurodegenerative disease characterized by progressive changes in behavior, personality, and/or language. CHCHD10 mutations are a relatively rare cause of FTLD, but their identification has provided valuable insights into the disease mechanisms.
-
Amyotrophic lateral sclerosis (ALS): A progressive neurodegenerative disease affecting motor neurons, leading to muscle weakness, paralysis, and ultimately, death. CHCHD10 mutations are estimated to account for a small percentage of familial ALS cases.
-
Spinal muscular atrophy (SMA): A genetic disorder characterized by the degeneration of motor neurons, leading to muscle weakness and atrophy. Certain variants in CHCHD10 have been linked to SMA-like phenotypes.
-
Mitochondrial myopathy: A group of disorders affecting muscle function due to mitochondrial dysfunction. CHCHD10 mutations can disrupt mitochondrial respiration and energy production in muscle tissue.
The CHCHD10 protein is believed to function as a structural component of the mitochondrial contact site and cristae organizing system (MICOS) complex, which is essential for maintaining the architecture of mitochondrial cristae and regulating the exchange of proteins and lipids between the inner and outer mitochondrial membranes. Disruption of CHCHD10 function can impair MICOS complex assembly and lead to mitochondrial dysfunction, contributing to the pathogenesis of associated neurological disorders.
Further research is ongoing to fully elucidate the precise role of CHCHD10 in mitochondrial biology and the mechanisms by which CHCHD10 mutations cause neurodegeneration and other diseases. Understanding these mechanisms may lead to the development of therapeutic strategies for these currently incurable conditions.