Abstract：
Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non-autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.
摘要：
巨自噬(以下称为自噬)是一种进化上保守的细胞过程,长期以来一直被认为是维持细胞稳态的细胞内机制。它涉及一种称为自噬体的膜状结构的形成，它将包括有毒蛋白质聚集体和功能失调的细胞器在内的货物运送到溶酶体进行降解和回收。自噬主要被认为是一种细胞自主机制。然而,最近的研究揭示了自噬的一个被低估的方面，即，非自主调节的自噬。非自主调节的自噬涉及自噬成分的降解，包括细胞器,cargo,和信号分子，并且在邻近细胞中由来自原代相邻或远处细胞/组织/器官的信号诱导。这篇综述提供了有关非自主调节自噬的复杂分子机制的见解。突出组织/器官内细胞或不同组织/器官中不同细胞类型之间的动态相互作用。重点放在包括分泌分子的细胞间通讯模式上，包括microRNA,以及它们在协调这一现象中的调节作用。此外，我们探讨了非自主调节的自噬在各种生理环境中的多维作用，跨越组织发育和衰老，以及它在不同病理条件下的重要性，包括癌症和神经变性.通过研究非自主调节的自噬的复杂性，我们希望深入了解多细胞生物体内复杂的细胞间动力学，包括哺乳动物。这些研究将揭示治疗干预以调节改变的人类生理学中的细胞间自噬途径的新途径。
