Seglen P O, Bohley P
Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo, Norway.
Experientia. 1992 Feb 15;48(2):158-72. doi: 10.1007/BF01923509.
Autophagic degradation of cytoplasm (including protein, RNA etc.) is a non-selective bulk process, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lives. The initial autophagic sequestration step, performed by a poorly-characterized organelle called a phagophore, is subject to feedback inhibition by purines and amino acids, the effect of the latter being potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive alpha 1-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid. Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, on intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy to a variable extent, and that the amphisome may play a central role as a collecting station for material destined for lysosomal degradation. Protein degradation can also take place in a 'salvage compartment' closely associated with the endoplasmic reticulum (ER). In this compartment unassembled protein chains are degraded by uncharacterized proteinases, while resident proteins return to the ER and assembled secretory and membrane proteins proceed through the Golgi apparatus. In the trans-Golgi network some proteins are proteolytically processed by Ca(2+)-dependent proteinases; furthermore, this compartment sorts proteins to lysosomes, various membrane domains, endosomes or secretory vesicles/granules. Processing of both endogenous and exogenous proteins can occur in endosomes, which may play a particularly important role in antigen processing and presentation. Proteins in endosomes or secretory compartments can either be exocytosed, or channeled to lysosomes for degradation. The switch mechanisms which decide between these options are subject to bioregulation by external agents (hormones and growth factors), and may play an important role in the control of protein uptake and secretion.
细胞质（包括蛋白质、RNA等）的自噬降解是一个非选择性的整体过程，超微结构证据以及不同半衰期的各种胞质酶自噬隔离速率的相似性都表明了这一点。自噬的初始隔离步骤由一种特征不明的细胞器——吞噬泡执行，该步骤受到嘌呤和氨基酸的反馈抑制，胰岛素可增强氨基酸的这种作用，而胰高血糖素则起拮抗作用。肾上腺素和其他肾上腺素能激动剂通过一种对哌唑嗪敏感的α1 - 肾上腺素能机制抑制自噬隔离。如环核苷酸类似物、磷酸二酯酶抑制剂和冈田酸的作用所示，cAMP和蛋白质磷酸化也会抑制隔离。天冬酰胺特异性抑制自噬 - 溶酶体融合，而对自噬隔离、溶酶体内降解或内吞途径没有任何显著影响。在天冬酰胺存在的情况下，积聚在溶酶体前液泡中的自噬物质可被内吞酶作用，这揭示了一种双功能细胞器——兼性自噬体的存在。来自几种细胞类型的证据表明，内吞作用可能在不同程度上与自噬相关联，并且兼性自噬体可能作为运往溶酶体降解物质的收集站发挥核心作用。蛋白质降解也可在与内质网（ER）紧密相关的“挽救区室”中发生。在这个区室中，未组装的蛋白质链被特性不明的蛋白酶降解，而驻留蛋白返回内质网，已组装的分泌蛋白和膜蛋白则通过高尔基体。在反式高尔基体网络中，一些蛋白质被钙依赖性蛋白酶进行蛋白水解加工；此外，这个区室将蛋白质分选到溶酶体、各种膜结构域、内体或分泌小泡/颗粒中。内体中可发生内源性和外源性蛋白质的加工，这在内抗原加工和呈递中可能起特别重要的作用。内体或分泌区室中的蛋白质既可以被胞吐，也可以被导向溶酶体进行降解。决定这些选择的转换机制受到外部因子（激素和生长因子）的生物调节，并且可能在蛋白质摄取和分泌的控制中起重要作用。
