Suclg1, encoding the alpha subunit of succinate-CoA ligase, is a key enzyme in the tricarboxylic acid cycle. It is involved in maintaining mitochondrial DNA (mtDNA) integrity and stability, and plays a crucial role in mitochondrial function, which is essential for energy production in cells. Mutations in Suclg1 are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9) and mitochondrial encephalomyopathies, highlighting its importance in human health [2,3,4,5].

Genetic depletion of Suclg1 significantly delays disease progression in mouse and humanized leukemia models. This indicates that Suclg1 promotes leukemia progression by restricting succinyl-CoA levels to suppress the succinylation of mitochondrial RNA polymerase (POLRMT), maintaining mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation [1]. In addition, in plexiform neurofibroma, knockdown of Suclg1 can inhibit the proliferation, migration of tumor cells, and enhance apoptosis, suggesting it promotes the pathogenesis of plexiform neurofibroma by enhancing cell aerobic respiration [6].

In conclusion, Suclg1 is essential for mitochondrial function and mtDNA maintenance. Studies using gene-knockout models, such as in leukemia and plexiform neurofibroma, have revealed its role in promoting disease progression. These findings help us understand the biological functions of Suclg1 in disease-related processes, providing potential therapeutic targets for these diseases.

References:

1. Yan, Weiwei, Xie, Chengmei, Sun, Sijun, Xu, Shuangnian, Wang, Yi-Ping. 2024. SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression. In The EMBO journal, 43, 2337-2367. doi:10.1038/s44318-024-00101-9. https://pubmed.ncbi.nlm.nih.gov/38649537/

2. Molaei Ramsheh, Samira, Erfanian Omidvar, Maryam, Tabasinezhad, Maryam, Salmani, Tayyeb Ali, Ghaedi, Hamid. 2020. SUCLG1 mutations and mitochondrial encephalomyopathy: a case study and review of the literature. In Molecular biology reports, 47, 9699-9714. doi:10.1007/s11033-020-05999-y. https://pubmed.ncbi.nlm.nih.gov/33230783/

3. El-Hattab, Ayman W, Craigen, William J, Scaglia, Fernando. 2017. Mitochondrial DNA maintenance defects. In Biochimica et biophysica acta. Molecular basis of disease, 1863, 1539-1555. doi:10.1016/j.bbadis.2017.02.017. https://pubmed.ncbi.nlm.nih.gov/28215579/

4. Chen, Yi-Ming, Chen, Wei, Xu, Yue, Shi, Jiaming, Wang, Dan. 2022. Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome-9. In Molecular genetics & genomic medicine, 10, e2010. doi:10.1002/mgg3.2010. https://pubmed.ncbi.nlm.nih.gov/35762302/

5. El-Hattab, Ayman W, Scaglia, Fernando. . Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options. In Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 10, 186-98. doi:10.1007/s13311-013-0177-6. https://pubmed.ncbi.nlm.nih.gov/23385875/

6. Zhou, Zifu, Li, Qingfeng, Huo, Ran. 2025. SUCLG1 promotes aerobic respiration and progression in plexiform neurofibroma. In International journal of oncology, 66, . doi:10.3892/ijo.2024.5716. https://pubmed.ncbi.nlm.nih.gov/39749698/