Pdhb-flox Mouse

Pdhb, also known as pyruvate dehydrogenase E1 subunit beta, is a nuclear-encoded pyruvate dehydrogenase. It catalyzes the conversion of pyruvate to acetyl coenzyme A, linking glycolysis and the tricarboxylic acid (TCA) cycle, and is thus crucial for cellular energy metabolism [1].

In clear cell renal cell carcinoma (ccRCC), knockdown of Pdhb promotes cell proliferation, migration, and invasion, indicating its inhibitory role in ccRCC progression [1,5]. In muscle, Pdhb promotes myogenic differentiation, as knockdown or overexpression in C2C12 and HSkMC cells modulates the expression of muscle-related genes [2]. In peripheral nerve injury, knockdown of Pdhb inhibits neurite outgrowth of primary DRG neurons and axon regeneration of sciatic nerve, while overexpression promotes axonal regeneration, which depends on lactate for energy supply [3]. In hepatocellular carcinoma (HCC), overexpression of Pdhb drives tumor growth and metastasis, and mediates metabolic reprogramming to promote glycolysis-related gene transcription [4].

In conclusion, Pdhb is essential for energy metabolism and plays significant roles in multiple biological processes and disease conditions. Loss-of-function experiments in various cell models have revealed its tumor-suppressive role in ccRCC and its promoting roles in myogenic differentiation and peripheral axon regeneration, as well as its oncogenic role in HCC. These findings contribute to understanding the mechanisms of related diseases and may provide potential therapeutic targets.