Ogdh-flox Mouse

Ogdh, also known as oxoglutarate dehydrogenase, is the first rate-limiting E1 subunit of the OGDH complex (OGDHC). It is part of the tricarboxylic acid (TCA) cycle, catalyzing α-ketoglutarate (α-KG) to succinyl-CoA, playing a crucial role in glycometabolism. The TCA cycle is fundamental for energy production and also impacts various cellular processes [1,2,3].

In glioblastoma, loss of OGDH function by the drug CPI-613 was synthetically lethal with Bcl-xL inhibition in patient-derived xenografts and neurosphere GBM cultures, suggesting a potential treatment strategy [1]. Biallelic variants in OGDH cause a neurodevelopmental disorder with metabolic and movement abnormalities [2]. In classical swine fever virus infection, CSFV reduces OGDH protein levels, and OGDH overexpression inhibits CSFV proliferation while knockdown increases it, with OGDH regulating the AMPK-mTOR-autophagy pathway [3]. In gastric cancer, OGDH promotes cancer progression by enhancing mitochondrial function and activating the Wnt/β-catenin signaling pathway, and SIRT5 suppresses GC cell growth through desuccinylating OGDH [4,5]. In sepsis-induced acute lung injury, OGDH is highly expressed, and its down-regulation alleviates the injury, with OGDH acting through the MAPK pathway to release pro-inflammatory factors [6].

In conclusion, Ogdh is essential for the TCA cycle and glycometabolism. Studies using gene-related models have revealed its significant roles in various disease conditions such as glioblastoma, neurodevelopmental disorders, viral infections, gastric cancer, and sepsis-induced acute lung injury. Understanding Ogdh's functions provides potential targets for treating these diseases.