Zubkova Ekaterina, Kalinin Alexander, Bolotskaya Anastasya, Beloglazova Irina, Menshikov Mikhail
National Medical Research Centre of Cardiology Named after Academician E.I. Chazov, 121552 Moscow, Russia.
Faculty of Fundamental Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia.
Curr Issues Mol Biol. 2024 Mar 8;46(3):2209-2235. doi: 10.3390/cimb46030142.
The cellular secretome is pivotal in mediating intercellular communication and coordinating responses to stressors. Exosomes, initially recognized for their role in waste disposal, have now emerged as key intercellular messengers with significant therapeutic and diagnostic potential. Similarly, autophagy has transcended its traditional role as a waste removal mechanism, emerging as a regulator of intracellular communication pathways and a contributor to a unique autophagy-dependent secretome. Secretory authophagy, initiated by various stress stimuli, prompts the selective release of proteins implicated in inflammation, including leaderless proteins that bypass the conventional endoplasmic reticulum-Golgi secretory pathway. This reflects the significant impact of stress-induced autophagy on cellular secretion profiles, including the modulation of exosome release. The convergence of exosome biogenesis and autophagy is exemplified by the formation of amphisomes, vesicles that integrate autophagic and endosomal pathways, indicating their synergistic interplay. Regulatory proteins common to both pathways, particularly mTORC1, emerge as potential therapeutic targets to alter cellular secretion profiles involved in various diseases. This review explores the dynamic interplay between autophagy and exosome formation, highlighting the potential to influence the secretome composition. While the modulation of exosome secretion and cytokine preconditioning is well-established in regenerative medicine, the strategic manipulation of autophagy is still underexplored, presenting a promising but uncharted therapeutic landscape.
细胞分泌组在介导细胞间通讯和协调对应激源的反应中起关键作用。外泌体最初因其在废物处理中的作用而被认识，现在已成为具有重要治疗和诊断潜力的关键细胞间信使。同样，自噬已超越其作为废物清除机制的传统作用，成为细胞内通讯途径的调节因子和独特的自噬依赖性分泌组的促成因素。由各种应激刺激引发的分泌性自噬促使参与炎症的蛋白质选择性释放，包括绕过传统内质网-高尔基体分泌途径的无信号肽蛋白质。这反映了应激诱导的自噬对细胞分泌谱的重大影响，包括对外泌体释放的调节。外泌体生物发生和自噬的融合以两性体的形成为例，两性体是整合自噬和内体途径的囊泡，表明它们的协同相互作用。这两条途径共有的调节蛋白，特别是mTORC1，成为改变参与各种疾病的细胞分泌谱的潜在治疗靶点。本综述探讨了自噬与外泌体形成之间的动态相互作用，强调了影响分泌组组成的潜力。虽然外泌体分泌的调节和细胞因子预处理在再生医学中已得到充分确立，但自噬的策略性操纵仍未得到充分探索，呈现出一个有前景但未知的治疗领域。
