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 is associated with pathways related to mitochondrial function and metabolism [2,3,4]. Genetic models are valuable for studying its functions, as disruptions in Suclg1 can lead to various biological consequences.

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), thus maintaining mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation [1]. In addition, in a mouse model of cytokine storm syndrome, neutrophil-derived extracellular vesicles deliver miR-27a-3p which suppresses Suclg1 expression, leading to itaconate accumulation in macrophages and ameliorating the syndrome [5].

In conclusion, Suclg1 plays a crucial role in mitochondrial function, mainly through its impact on mtDNA transcription and mitochondrial biogenesis. Its function is closely related to leukemia progression and cytokine storm syndrome, as revealed by model-based research. Understanding Suclg1's role in these processes may provide new insights into treating related diseases.