Suclg2-flox Mouse

Suclg2, the succinyl-coenzyme A (CoA) synthetase GDP-forming subunit β, is involved in important metabolic processes. It participates in the tricarboxylic acid cycle by catalyzing the conversion of succinyl-CoA to succinate, generating GTP in the process. This function is crucial for mitochondrial energy production and maintaining normal cellular metabolism [3].

In lung adenocarcinoma, deletion of Suclg2 upregulates the succinylation level of mitochondrial proteins, inhibits key metabolic enzymes, and dampens mitochondrial function. Suclg2 itself is succinylated on Lys93, enhancing its protein stability, promoting cell proliferation and tumorigenesis [1].

In regulatory dendritic cells (diffDCs), Suclg2-interference impairs the tolerogenic function of diffDCs, enhances NF-κB signaling and expression of inflammatory genes, indicating its role in maintaining the immunoregulatory function of diffDCs [2].

In pheochromocytoma and paraganglioma, germline variants in Suclg2 lead to absence of its protein, decrease in SDHB subunit of SDH, faulty assembly of complex II, aberrant respiration, and elevated succinate accumulation [3].

In prostate cancer, ADT-induced upregulation of Suclg2 is associated with NE differentiation, and knockdown of Suclg2 suppresses NE differentiation and tumor growth [4].

In rheumatoid arthritis, SUCLG2-deficient T cells differentiate into pro-inflammatory effector cells, and preventing tubulin acetylation in these cells can inhibit synovitis [5].

In Alzheimer's disease, a single-nucleotide polymorphism in SUCLG2 is associated with CSF Aβ1-42 levels and rate of cognitive decline, and it is also included in the diagnostic panel for mild cognitive impairment [6,7].

In conclusion, Suclg2 plays essential roles in multiple biological processes and diseases. Its functions in mitochondrial metabolism, immune regulation, and tumorigenesis are revealed through various loss-of-function experiments. These findings contribute to understanding the mechanisms of diseases such as cancer, immune-related disorders, and neurodegenerative diseases, potentially providing new targets for treatment.