Suclg1, encoding the alpha subunit of succinate-CoA ligase/synthetase (SCS), is a key enzyme in the tricarboxylic acid cycle. It is involved in maintaining mitochondrial DNA (mtDNA) integrity and stability, and plays a role in regulating mitochondrial function, energy production, and cell metabolism [3,4,5].

In leukemia, FLT3-mutated cells upregulate Suclg1 expression. Suclg1 restricts succinyl-CoA levels, suppressing the succinylation of mitochondrial RNA polymerase (POLRMT). Genetic depletion of Suclg1 significantly delays disease progression in mouse and humanized leukemia models, indicating its importance in leukemia cell proliferation and mitobiogenesis [1].

In mitochondrial encephalomyopathy and mitochondrial DNA depletion syndrome-9, Suclg1 mutations lead to corresponding phenotypes, as seen in case studies where novel Suclg1 variants were identified [2,5].

In plexiform neurofibroma, Suclg1 promotes aerobic respiration and tumor cell progression by enhancing mitochondrial quality and fusion [6].

In conclusion, Suclg1 is essential for maintaining mitochondrial function and integrity, and its dysregulation is associated with various diseases, especially leukemia, mitochondrial encephalomyopathies, and plexiform neurofibroma. Studies using gene-knockout (KO) or conditional-knockout (CKO) mouse models, as well as patient-based case studies, have revealed its critical role in these disease conditions, providing potential therapeutic targets for future strategies.