Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
Center for Human Nutrition, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Biomolecules. 2023 Jan 31;13(2):261. doi: 10.3390/biom13020261.
Pyruvate sits at an important metabolic crossroads of intermediary metabolism. As a product of glycolysis in the cytosol, it must be transported into the mitochondrial matrix for the energy stored in this nutrient to be fully harnessed to generate ATP or to become the building block of new biomolecules. Given the requirement for mitochondrial import, it is not surprising that the mitochondrial pyruvate carrier (MPC) has emerged as a target for therapeutic intervention in a variety of diseases characterized by altered mitochondrial and intermediary metabolism. In this review, we focus on the role of the MPC and related metabolic pathways in the liver in regulating hepatic and systemic energy metabolism and summarize the current state of targeting this pathway to treat diseases of the liver. Available evidence suggests that inhibiting the MPC in hepatocytes and other cells of the liver produces a variety of beneficial effects for treating type 2 diabetes and nonalcoholic steatohepatitis. We also highlight areas where our understanding is incomplete regarding the pleiotropic effects of MPC inhibition.
丙酮酸处于中间代谢的重要代谢十字路口。作为细胞质糖酵解的产物，它必须被转运到线粒体基质中，以便充分利用这种营养物质中储存的能量来产生 ATP，或成为新生物分子的构建块。鉴于对线粒体输入的需求，线粒体丙酮酸载体 (MPC) 已成为各种特征为线粒体和中间代谢改变的疾病的治疗干预的靶点，这并不奇怪。在这篇综述中，我们重点关注 MPC 及其相关代谢途径在肝脏中调节肝和全身能量代谢中的作用，并总结了目前针对该途径治疗肝脏疾病的状态。现有证据表明，抑制肝细胞和肝脏其他细胞中的 MPC 可产生多种治疗 2 型糖尿病和非酒精性脂肪性肝炎的有益作用。我们还强调了我们对 MPC 抑制的多效性影响理解不完整的领域。
