CHCHD7 Human

The Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 7 (CHCHD7) protein is a member of the CHCHD protein family, which is characterized by the presence of a coiled-coil-helix-coiled-coil-helix (CHCH) domain. This domain is stabilized by disulfide bonds and plays a crucial role in the structural integrity and function of the protein. CHCHD7 is encoded by the CHCHD7 gene in humans and is involved in various cellular processes, particularly within the mitochondria.

The CHCH domain is a distinctive structural motif that consists of two helices connected by a loop, forming a coiled-coil structure. This domain is stabilized by disulfide bonds between cysteine residues, which are essential for maintaining the protein’s alpha-helical secondary structure. Reduction of these disulfide bonds, for instance by dithiothreitol (DTT), leads to the loss of the alpha-helical structure and subsequent aggregation and precipitation of the protein .

CHCHD7, like other CHCHD proteins, is primarily localized in the mitochondria, where it plays a significant role in maintaining mitochondrial function and integrity. The protein is involved in the regulation of mitochondrial metabolism, synthesis of respiratory chain components, and modulation of cell apoptosis. These functions are critical for cellular energy production and overall cellular health.

CHCHD7 and other CHCHD proteins are evolutionarily conserved and have been implicated in various physiological and pathophysiological processes. They are involved in maintaining the structural integrity of mitochondrial cristae, which are the folds within the inner mitochondrial membrane that increase the surface area for energy production. Proper functioning of these proteins is essential for efficient mitochondrial respiration and energy production.

Mutations in CHCHD proteins, including CHCHD7, have been associated with several neurodegenerative diseases. For example, mutations in CHCHD10, a closely related protein, have been linked to amyotrophic lateral sclerosis (ALS), frontotemporal lobe dementia (FTD), and other motor neuron diseases . These mutations often result in abnormal mitochondrial structure, deficiencies in respiratory chain complexes, impaired mitochondrial respiration, and multiple mitochondrial DNA deletions.

Given the critical roles of CHCHD proteins in mitochondrial function and their association with neurodegenerative diseases, they are considered potential therapeutic targets. Understanding the pathophysiological roles of these proteins can lead to the development of novel therapeutic strategies for treating diseases associated with mitochondrial dysfunction.

Recent research has focused on elucidating the specific functions of CHCHD7 and other CHCHD proteins, as well as their interactions with other mitochondrial proteins. This research is essential for developing targeted therapies that can modulate the activity of these proteins and restore normal mitochondrial function in disease states.