Sucla2, also known as succinyl-CoA synthetase ADP-forming subunit β, is a key component of succinyl-CoA ligase. It functions in the tricarboxylic acid (TCA) cycle, catalyzing the conversion of succinyl-CoA to succinate coupled with ADP phosphorylation. This process is crucial for energy production and maintaining mitochondrial function. Genetic models, such as KO mouse models, are valuable for studying its function [1,2,3].

A muscle-specific conditional knock-out (CKO) mouse model of Sucla2 was generated using the Cre-Lox system. Inactivation of Sucla2 in skeletal muscle led to reduced body weight, muscle weakness, and exercise intolerance. The soleus (SOL) muscle was more significantly impacted than the extensor digitorum longus (EDL) muscle, with reduced specific tetanic force, slower contraction and relaxation rates, and increased mitochondria in the SOL. This model provides insights into the muscle-specific and fiber-type-specific pathogenic mechanisms of SCS-deficient myopathy [2].

In conclusion, Sucla2 is essential for the TCA cycle and mitochondrial function. The Sucla2 CKO mouse model has been instrumental in understanding the role of Sucla2 in mitochondrial myopathy, revealing muscle-specific phenotypes that contribute to our understanding of the disease mechanism.