Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Medical Genetics, Department of Translational Medicine, Federico II University, Naples, Italy Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, USA.
EMBO Mol Med. 2016 Feb 1;8(2):73-6. doi: 10.15252/emmm.201505966.
In the early 50s, Christian De Duve identified a new cellular structure, the lysosome, defined as the cell's “suicide bag” (de Duve, 2005). Sixty years later, it is clear that the lysosome greatly exceeded the expectations of its discoverer. Over 50 different types of lysosomal storage diseases have been identified, each due to the deficiency or malfunction of a specific lysosomal protein. In addition, an important role of the lysosome has been unveiled in several common human diseases, such as cancer, obesity, neurodegenerative diseases, and infection. Recent studies have led to the identification of a lysosome‐to‐nucleus signaling pathway and a lysosomal gene network that regulate cellular clearance and energy metabolism. These observations have opened a completely new field of research and changed our traditional view of the lysosome from a dead‐end organelle to a control center of cell metabolism. An important challenge for the future will be to exploit these discoveries to identify modulators of lysosomal function that may be used to treat human diseases.
在上世纪 50 年代早期,克里斯蒂安·德迪夫(Christian De Duve)发现了一种新的细胞结构,溶酶体,并将其定义为细胞的“自杀袋”(de Duve,2005)。六十年后,溶酶体的重要性远远超出了发现者的预期。目前已经发现了超过 50 种不同类型的溶酶体贮积症,每种疾病都是由于特定溶酶体蛋白的缺乏或功能障碍所致。此外,溶酶体在几种常见的人类疾病中也发挥着重要作用,如癌症、肥胖、神经退行性疾病和感染。最近的研究揭示了溶酶体-核信号通路和溶酶体基因网络,它们调节细胞的清除和能量代谢。这些观察结果开辟了一个全新的研究领域,并改变了我们对溶酶体作为一个终末细胞器的传统认识,将其重新定义为细胞代谢的控制中心。未来的一个重要挑战将是利用这些发现来鉴定溶酶体功能的调节剂,这些调节剂可能被用于治疗人类疾病。