The impacts of the mitochondrial myopathy-associated G58R mutation on the dynamic structural properties of CHCHD10

The mitochondria are responsible for producing energy within the cell, and in mitochondrial myopathy, there is a defect in the energy production process. The CHCHD10 gene codes for a protein called coiled-coil-helix-coiled-coil-helix domain-containing protein 10 (CHCHD10), which is found in the mitochondria and is involved in the regulation of mitochondrial function. G58R mutation has been shown to disrupt the normal function of CHCHD10, leading to mitochondrial dysfunction and ultimately to the development of mitochondrial myopathy. The structures of G58R mutant CHCHD10 and how G58R mutation impacts the wild-type CHCHD10 protein at the monomeric level are unknown. To address this problem, we conducted homology modeling, multiple run molecular dynamics simulations and bioinformatics calculations. We represent herein the structural ensemble properties of the G58R mutant CHCHD10 (CHCHD10(G58R)) in aqueous solution. Moreover, we describe the impacts of G58R mutation on the structural ensembles of wild-type CHCHD10 (CHCHD10(WT)) in aqueous solution. The dynamics properties as well as structural properties of CHCHD10(WT) are impacted by the mitochondrial myopathy-related G58R mutation. Specifically, the secondary and tertiary structure properties, root mean square fluctuations, Ramachandran diagrams and results from principal component analysis demonstrate that the CHCHD10(WT) and CHCHD10(G58R) proteins possess different structural ensemble characteristics and describe the impacts of G58R mutation on CHCHD10(WT). These findings may be helpful for designing new treatments for mitochondrial myopathy.Communicated by Ramaswamy H. Sarma

Automated summary

The mitochondria are responsible for energy production within the cell, and defects in this process can lead to mitochondrial myopathy. The CHCHD10 gene codes for a protein involved in mitochondrial function, and a specific mutation known as G58R has been found to disrupt its normal function and contribute to mitochondrial dysfunction and the development of mitochondrial myopathy. This study used modeling and simulations to explore the structural characteristics and impacts of the G58R mutation on CHCHD10(WT). The findings provide insights into the structural differences and effects of the G58R mutation, which could contribute to the development of new treatments for mitochondrial myopathy.