Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cells. 2024 Jul 25;13(15):1253. doi: 10.3390/cells13151253.
Mitochondria are crucial for cellular ATP production. They are highly dynamic organelles, whose morphology and function are controlled through mitochondrial fusion and fission. The specific roles of mitochondria in podocytes, the highly specialized cells of the kidney glomerulus, remain less understood. Given the significant structural, functional, and molecular similarities between mammalian podocytes and nephrocytes, we employed fly nephrocytes to explore the roles of mitochondria in cellular function. Our study revealed that alterations in the Pink1-Park (mammalian PINK1-PRKN) pathway can disrupt mitochondrial dynamics in nephrocytes. This disruption led to either fragmented or enlarged mitochondria, both of which impaired mitochondrial function. The mitochondrial dysfunction subsequently triggered defective intracellular endocytosis, protein aggregation, and cellular damage. These findings underscore the critical roles of mitochondria in nephrocyte functionality.
线粒体对于细胞 ATP 的产生至关重要。它们是高度动态的细胞器，其形态和功能通过线粒体融合和裂变来控制。线粒体在足细胞中的具体作用（肾脏肾小球的高度特化细胞）仍知之甚少。鉴于哺乳动物足细胞和肾细胞之间存在显著的结构、功能和分子相似性，我们利用果蝇肾细胞来探索线粒体在细胞功能中的作用。我们的研究表明，Pink1-Park（哺乳动物 PINK1-PRKN）通路的改变会破坏肾细胞中线粒体的动态。这种破坏导致线粒体碎片化或增大，两者都损害了线粒体的功能。线粒体功能障碍随后引发了缺陷的细胞内吞作用、蛋白质聚集和细胞损伤。这些发现强调了线粒体在肾细胞功能中的关键作用。
