Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC.
Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL.
Exp Eye Res. 2013 Nov;116:141-50. doi: 10.1016/j.exer.2013.08.017. Epub 2013 Sep 4.
The eye lens consists of a layer of epithelial cells that overlay a series of differentiating fiber cells that upon maturation lose their mitochondria, nuclei and other organelles. Lens transparency relies on the metabolic function of mitochondria contained in the lens epithelial cells and in the immature fiber cells and the programmed degradation of mitochondria and other organelles occurring upon lens fiber cell maturation. Loss of lens mitochondrial function in the epithelium or failure to degrade mitochondria and other organelles in lens fiber cells results in lens cataract formation. To date, the mechanisms that govern the maintenance of mitochondria in the lens and the degradation of mitochondria during programmed lens fiber cell maturation have not been fully elucidated. Here, we demonstrate using electron microscopy and dual-label confocal imaging the presence of autophagic vesicles containing mitochondria in lens epithelial cells, immature lens fiber cells and during early stages of lens fiber cell differentiation. We also show that mitophagy is induced in primary lens epithelial cells upon serum starvation. These data provide evidence that autophagy occurs throughout the lens and that mitophagy functions in the lens to remove damaged mitochondria from the lens epithelium and to degrade mitochondria in the differentiating lens fiber cells for lens development. The results provide a novel mechanism for how mitochondria are maintained to preserve lens metabolic function and how mitochondria are degraded upon lens fiber cell maturation.
晶状体由一层覆盖着一系列分化纤维细胞的上皮细胞组成,这些纤维细胞在成熟后会失去线粒体、细胞核和其他细胞器。晶状体的透明性依赖于包含在晶状体上皮细胞和未成熟纤维细胞中的线粒体的代谢功能,以及在晶状体纤维细胞成熟时发生的线粒体和其他细胞器的程序性降解。上皮细胞中线粒体功能的丧失或晶状体纤维细胞中线粒体和其他细胞器的降解失败会导致晶状体白内障的形成。迄今为止,控制晶状体中线粒体的维持和程序性晶状体纤维细胞成熟过程中线粒体降解的机制尚未完全阐明。在这里,我们使用电子显微镜和双标记共聚焦成像技术证明,在晶状体上皮细胞、未成熟的晶状体纤维细胞以及晶状体纤维细胞分化的早期阶段,存在含有线粒体的自噬小泡。我们还表明,血清饥饿会诱导原代晶状体上皮细胞发生线粒体自噬。这些数据提供了证据表明自噬发生在整个晶状体中,并且线粒体自噬在晶状体中起作用,从晶状体上皮细胞中去除受损的线粒体,并在分化的晶状体纤维细胞中降解线粒体,以促进晶状体发育。该结果为研究如何维持线粒体以保持晶状体代谢功能,以及如何在晶状体纤维细胞成熟时降解线粒体提供了新的机制。