INSERM U984, Faculty of Pharmacy, University Paris-Sud 11, 92296 Châtenay-Malabry Cedex, France.
Int J Biochem Cell Biol. 2011 Apr;43(4):460-4. doi: 10.1016/j.biocel.2011.01.006. Epub 2011 Jan 20.
The autophagosome is a double-membrane bound compartment that initiates macroautophagy, a degradative pathway for cytoplasmic material terminating in the lysosomal compartment. The discovery of ATG genes involved in the formation of autophagosomes has greatly increased our understanding of the molecular basis of macroautophagy, and its role in cell function. Macroautophagy plays a pivotal role in cell fitness by removing obsolete organelles and protein aggregates. Its stimulation is an adaptive response to stressful situations, such as nutrient deprivation, intended to maintain a level of ATP compatible with cell survival. Macroautophagy is central for organ homeostasis, embryonic development, and longevity. Malfunctioning autophagy is observed in many human diseases including cancer, neurodegenerative diseases, cardiac and muscular diseases, infectious and inflammatory diseases, diabetes, and obesity. Discovering potential drug therapies that can be used to modulate macroautophagy is a major challenge, and likely to enhance the therapeutic arsenal against many human diseases.
自噬体是双层膜结合的隔室，它起始巨自噬作用，这是一种细胞质物质的降解途径，最终终止于溶酶体隔室。参与自噬体形成的 ATG 基因的发现极大地提高了我们对巨自噬作用的分子基础及其在细胞功能中的作用的理解。巨自噬通过去除衰老的细胞器和蛋白聚集体在细胞适应性中起着关键作用。其刺激是对营养缺乏等应激情况的适应性反应，旨在维持与细胞存活兼容的 ATP 水平。巨自噬对器官稳态、胚胎发育和长寿至关重要。在包括癌症、神经退行性疾病、心脏和肌肉疾病、传染病和炎症性疾病、糖尿病和肥胖症在内的许多人类疾病中都观察到自噬作用的功能障碍。发现可用于调节巨自噬作用的潜在药物疗法是一个重大挑战，可能会增强对抗许多人类疾病的治疗手段。
