Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kidney360. 2020 Sep 24;1(9):982-992. doi: 10.34067/kid.0002352020.
Mitochondrial medicine has experienced significant progress in recent years and is expected to grow significantly in the near future, yielding many opportunities to translate novel bench discoveries into clinical medicine. Multiple lines of evidence have linked mitochondrial dysfunction to a variety of metabolic diseases, including diabetic nephropathy (DN). Mitochondrial dysfunction presumably precedes the emergence of key histologic and biochemical features of DN, which provides the rationale to explore mitochondrial fitness as a novel therapeutic target in patients with DN. Ultimately, the success of mitochondrial medicine is dependent on a better understanding of the underlying biology of mitochondrial fitness and function. To this end, recent advances in mitochondrial biology have led to new understandings of the potential effect of mitochondrial dysfunction in a myriad of human pathologies. We have proposed that molecular mechanisms that modulate mitochondrial dynamics contribute to the alterations of mitochondrial fitness and progression of DN. In this comprehensive review, we highlight the possible effects of mitochondrial dysfunction in DN, with the hope that targeting specific mitochondrial signaling pathways may lead to the development of new drugs that mitigate DN progression. We will outline potential tools to improve mitochondrial fitness in DN as a novel therapeutic strategy. These emerging views suggest that the modulation of mitochondrial fitness could serve as a key target in ameliorating progression of kidney disease in patients with diabetes.
近年来,线粒体医学取得了重大进展,预计在不久的将来会有显著增长,为将新的基础发现转化为临床医学提供了许多机会。有多种证据表明,线粒体功能障碍与多种代谢疾病有关,包括糖尿病肾病(DN)。线粒体功能障碍可能先于 DN 的关键组织学和生化特征出现,这为探索线粒体适应性作为 DN 患者的新治疗靶点提供了依据。最终,线粒体医学的成功取决于对线粒体适应性和功能的基础生物学的更好理解。为此,线粒体生物学的最新进展使人们对线粒体功能障碍在多种人类疾病中的潜在影响有了新的认识。我们提出,调节线粒体动力学的分子机制有助于改变线粒体适应性并促进 DN 的进展。在这篇全面的综述中,我们强调了线粒体功能障碍在 DN 中的可能作用,希望针对特定的线粒体信号通路可能会开发出减轻 DN 进展的新药。我们将概述改善 DN 中线粒体适应性的潜在工具,作为一种新的治疗策略。这些新出现的观点表明,调节线粒体适应性可以作为改善糖尿病患者肾脏疾病进展的关键靶点。