Rangos Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, USA.
Department of Pediatrics, Division of Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Pediatr Nephrol. 2020 Jan;35(1):1-8. doi: 10.1007/s00467-018-4157-2. Epub 2018 Dec 15.
The mammalian kidney is a complex organ that has several metabolically active cell types to aid in waste filtration, salt-water balance, and electrolyte homeostasis in the body. These functions are done primarily through the nephron, which relies on strict regulation of various metabolic pathways. Any deviations in the metabolic profile of nephrons or their precursor cells called nephron progenitors can lead to renal pathologies and abnormal development. Metabolism encompasses the mechanisms by which cells generate intermediate molecules and energy in the form of adenosine triphosphate (ATP). ATP is required by all cells and is mainly generated through glycolysis, fatty acid oxidation, and oxidative phosphorylation. During kidney development, self-renewing or proliferating cells rely on glycolysis to a greater extent than the other metabolic pathways to supply energy, replenish reducing equivalents, and generate nucleotides. However, terminally differentiated cell types rely more heavily on fatty acid oxidation and oxidative phosphorylation performed in the mitochondria to fulfill energy requirements. Further, the mature nephron is comprised of distinct segments and each segment utilizes metabolic pathways to varying degrees depending on the specific function. This review will focus on major metabolic processes performed by the nephron during health and disease.
哺乳动物的肾脏是一个复杂的器官,具有几种代谢活跃的细胞类型,有助于废物过滤、盐水平衡和体内电解质稳态。这些功能主要通过依赖于各种代谢途径严格调节的肾单位来完成。肾单位或其前体细胞(称为肾祖细胞)的代谢特征的任何偏差都可能导致肾脏病变和异常发育。代谢包括细胞以三磷酸腺苷 (ATP) 的形式产生中间分子和能量的机制。所有细胞都需要 ATP,它主要通过糖酵解、脂肪酸氧化和氧化磷酸化产生。在肾脏发育过程中,自我更新或增殖的细胞比其他代谢途径更依赖糖酵解来提供能量、补充还原当量和产生核苷酸。然而,终末分化的细胞类型更依赖于在线粒体中进行的脂肪酸氧化和氧化磷酸化来满足能量需求。此外,成熟的肾单位由不同的节段组成,每个节段根据特定的功能,利用代谢途径的程度也不同。这篇综述将重点介绍肾单位在健康和疾病状态下进行的主要代谢过程。