Ogdhl-flox Mouse

Oxoglutarate dehydrogenase-like (OGDHL) is an isoenzyme of oxyglutarate dehydrogenase (OGDH) in the OGDH complex. It is involved in degrading glucose and glutamate, and plays a role in regulating glutamine metabolism, which is crucial for maintaining normal cellular metabolism and energy production [1,4]. It is also associated with important cellular pathways such as the tricarboxylic acid cycle [1].

In hepatocellular carcinoma (HCC), OGDHL knockdown promotes tumor cell proliferation, while overexpression inhibits growth in mouse xenograft models. OGDHL down-regulation leads to an up-regulation of the α-ketoglutarate (αKG):citrate ratio, driving reductive carboxylation of glutamine-derived αKG via retrograde tricarboxylic acid cycling and activating the mTORC1 signaling pathway in an αKG-dependent manner, thus promoting de novo lipogenesis [1]. In clear cell renal cell carcinoma (ccRCC), upregulation of OGDHL expression effectively inhibits ccRCC growth and metastasis both in vitro and in vivo [2]. In kidney renal clear cell carcinoma (KIRC), low OGDHL expression is associated with tumor progression and poor prognosis, and is related to differences in the proportion of tumor-infiltrating immune cells [3].

In conclusion, OGDHL is essential for normal cellular metabolism, especially in glutamine metabolism. Gene knockout or knockdown models in mice have revealed its tumor-suppressive role in multiple cancers such as HCC, ccRCC, and KIRC. Understanding the function of OGDHL through these models provides potential prognostic biomarkers and therapeutic targets for these cancer types [1,2,3].