SDHA, also known as succinate dehydrogenase subunit A, is a key component of the succinate dehydrogenase complex. This complex is involved in the tricarboxylic acid (TCA) cycle and mitochondrial electron transport chain, playing a crucial role in cellular energy metabolism. Dysfunction in the SDH complex can have far-reaching impacts on cellular function and is associated with various biological processes and disease states [1,2,3,4,5].

SDHA-related mutations are associated with several diseases. In 20-40% of KIT/PDGFRA-negative gastrointestinal stromal tumors (GISTs) with SDH-deficiency, approximately 30% have SDHA mutations, leading to loss of SDHA and SDHB protein expression [1]. In paraganglioma and phaeochromocytoma, SDHA pathogenic germline variants are identified in up to 10% of patients, and in up to 30% of wild-type gastrointestinal stromal tumours [2]. SDHA-related phaeochromocytomas and paragangliomas occur across a wide age range, with 25.5% of cases having metastatic disease, commonly to bone and lymph nodes [3]. Also, reduction of SDHA/B promotes hepatocellular carcinoma by stabilizing YAP/TAZ through modulating cullin1 NEDDylation [4].

In conclusion, SDHA is essential for normal cellular energy metabolism through its role in the SDH complex. Research on SDHA-related gene mutations in various disease models, such as in GISTs, paraganglioma, phaeochromocytoma, and hepatocellular carcinoma, has revealed its significant contribution to disease development. Understanding SDHA's function and its associated mutations can provide insights into disease mechanisms and potentially guide new therapeutic strategies.