INSERM, U848, Villejuif, France.
Sci Signal. 2010 Jun 1;3(124):pe19. doi: 10.1126/scisignal.3124pe19.
During autophagy, portions of the cytoplasm are sequestered into autophagosomes and digested by lysosomal hydrolases. Massive autophagy can be induced in mammalian tissues in a coordinated fashion through nutrient deprivation, which has prompted the search of soluble metabolites that can stimulate autophagy. Ammonia, which is generated as a by-product of glutaminolysis, has been identified as a diffusible factor that stimulates autophagy. Intriguingly, cancer cells increase the rate glutaminolysis and the interstitial fluid of cancers contains higher-than-normal physiological concentrations of ammonia, suggesting a previously unknown pathway through which tumor cells can condition their microenvironment.
在自噬过程中，细胞质的一部分被隔离到自噬体中，并被溶酶体水解酶消化。通过营养剥夺，可以协调一致地诱导哺乳动物组织中的巨大多泡体自噬，这促使人们寻找可以刺激自噬的可溶性代谢物。氨是谷氨酰胺分解的副产物，已被确定为一种可扩散因子，可刺激自噬。有趣的是，癌细胞增加了谷氨酰胺分解的速度，而癌症的细胞间质中氨的生理浓度高于正常水平，这表明肿瘤细胞可以通过一种未知的途径来调节其微环境。
