Longo Agostina, Manganelli Valeria, Misasi Roberta, Riitano Gloria, Caglar Tuba Rana, Fasciolo Elena, Recalchi Serena, Sorice Maurizio, Garofalo Tina
Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Cells. 2025 May 20;14(10):749. doi: 10.3390/cells14100749.
Autophagy and apoptosis are two essential mechanisms regulating cell fate. Although distinct, their signaling pathways are closely interconnected through various crosstalk mechanisms. Lipid rafts are described to act as both physical and functional platforms during the early stages of autophagic and apoptotic processes. Only recently has a role for lipid raft-associated molecules in regulating EV biogenesis and release begun to emerge. In particular, lipids of EV membranes are essential components in conferring stability to these vesicles in different extracellular environments and/or to facilitate binding or uptake into recipient cells. In this review we highlight these aspects, focusing on the role of lipid molecules during apoptosis and secretory autophagy pathways. We describe the molecular machinery that connects autophagy and apoptosis with vesicular trafficking and lipid metabolism during the release of EVs, and how their alterations contribute to the development of various diseases, including autoimmune disorders and cancer. Overall, these findings emphasize the complexity of autophagy/apoptosis crosstalk and its key role in cellular dynamics, supporting the role of lipid rafts as new therapeutic targets.
自噬和凋亡是调节细胞命运的两种基本机制。尽管二者不同，但它们的信号通路通过各种相互作用机制紧密相连。脂质筏被描述为在自噬和凋亡过程的早期阶段充当物理和功能平台。直到最近，脂质筏相关分子在调节细胞外囊泡生物发生和释放中的作用才开始显现。特别是，细胞外囊泡膜的脂质是使这些囊泡在不同细胞外环境中保持稳定和/或促进其与受体细胞结合或被摄取的重要成分。在本综述中，我们重点介绍这些方面，聚焦于脂质分子在凋亡和分泌性自噬途径中的作用。我们描述了在细胞外囊泡释放过程中连接自噬、凋亡与囊泡运输和脂质代谢的分子机制，以及这些机制的改变如何导致包括自身免疫性疾病和癌症在内的各种疾病的发生。总体而言，这些发现强调了自噬/凋亡相互作用的复杂性及其在细胞动态变化中的关键作用，支持脂质筏作为新治疗靶点的作用。
