Department of Internal Medicine I, University Clinic of Tübingen, Tübingen, Germany.
Mol Cell Biol. 2012 Jan;32(1):2-11. doi: 10.1128/MCB.06159-11. Epub 2011 Oct 24.
Living cells are adaptive self-sustaining systems. They strictly depend on the sufficient supply of oxygen, energy, and nutrients from the outside in order to sustain their internal organization. However, as autonomous entities they are able to monitor and appropriately adapt to any critical fluctuation in their environment. In the case of insufficient external nutrient supply or augmented energy demands, cells start to extensively digest their own interior. This process, known as macroautophagy, comprises the transport of cytosolic portions and entire organelles to the lysosomal compartment via specific double-membrane vesicles, called autophagosomes. Although extensively upregulated under nutrient restriction, a low level of basal autophagy is likewise crucial in order to sustain the cellular homeostasis. On the other hand, cells have to avoid excessive and enduring self-digestion. The delicate balance between external energy and nutrient supply and internal production and consumption is a demanding task. The complex protein network that senses and precisely reacts to environmental changes is thus mainly regulated by rapid and reversible posttranslational modifications such as phosphorylation. This review focuses on the serine/threonine protein kinases AMP-activated protein kinase, mammalian target of rapamycin (mTOR), and unc-51-like kinase 1/2 (Ulk1/2), three interconnected major junctions within the autophagy regulating signaling network.
活细胞是自适应的自维持系统。它们严格依赖于从外部充分供应氧气、能量和营养物质，以维持其内部组织。然而，作为自主实体，它们能够监测并适当地适应其环境中的任何关键波动。在外部营养供应不足或能量需求增加的情况下，细胞开始广泛地消化自身内部。这个过程被称为巨自噬，包括通过特定的双层囊泡（自噬体）将细胞质部分和整个细胞器运输到溶酶体隔室。尽管在营养限制下广泛上调，但基础自噬的低水平对于维持细胞内稳态同样至关重要。另一方面，细胞必须避免过度和持久的自我消化。外部能量和营养供应与内部产生和消耗之间的微妙平衡是一项艰巨的任务。因此，感知和精确反应环境变化的复杂蛋白质网络主要受到快速和可逆的翻译后修饰（如磷酸化）的调节。这篇综述重点介绍了丝氨酸/苏氨酸蛋白激酶 AMP 激活的蛋白激酶、哺乳动物雷帕霉素靶蛋白（mTOR）和 UNC-51 样激酶 1/2（Ulk1/2），它们是自噬调节信号网络中的三个相互连接的主要节点。
