Metabolic regulation of exosome biogenesis

项目摘要/摘要 Exosome是直径50-200 nm的纳米级小泡，由不同类型的细胞在体内活跃地分泌 我们的身体。当它们携带亲代细胞特有的生物分子(例如蛋白质、RNA或代谢物)时 很容易在生物体液(如血液或尿液)中发现，外切体已成为一种有希望的生物标志物。 各种疾病的检测和治疗监测。此外，外切体也有很强的潜力作为 再生和免疫调节的治疗剂；例如，来自间充质干细胞的外切体 干细胞(MSCs)已经在治疗脑损伤的临床试验中进行了测试。然而，最根本的是 细胞分泌外切体的机制以及外切体中的分子含量是如何 决心仍然不清楚；例如，我们关于如何监管MSCs以最大限度地 产生携带治疗分子的外切体。我的实验室旨在通过以下方式解决这些问题 研究代谢在外切体生物发生中的作用，因为外切体生物发生的多个步骤， 包括在细胞内形成小泡并融合到质膜中，都直接与 代谢过程。在这个项目中，我们将研究外切体的生成率和分子 含量是在不同的代谢条件下测定的，特别是在营养物质和 NAD水平。我们还将开发一种基于囊泡内蛋白和 研究线粒体应激条件下具有线粒体分子的外切体的生物发生。 该项目的研究成果将加深我们对外显体的理解，并帮助我们 更有效地开发基于外切体的诊断和治疗策略。我们的长期研究目标是 探讨细胞外小泡(EVS)代谢与生物发生相互作用的机制。 米拉的这项研究重点是外显体，这是电动汽车的一个亚群。根据我们的研究进展，我们将 未来我们的研究范围将扩大到其他电动汽车，包括微囊。

Project Summary/Abstract Exosomes are nanoscale vesicles with a diameter of 50-200 nm, actively secreted by various types of cells in our body. As they carry biomolecules (e.g., proteins, RNAs, or metabolites) specific to their parental cells and are easily found in biofluids (e.g., blood or urine), exosomes have emerged as a promising biomarker for the detection and treatment monitoring of various diseases. Also, exosomes have the strong potential as a therapeutic agent for regeneration and immune regulation; for example, exosomes from mesenchymal stem cells (MSCs) have been tested in clinical trials for the treatment of brain injury. However, the fundamental mechanisms of what makes cells secrete exosomes and how the molecular contents in exosomes are determined remain unclear; for example, we have limited information about how to regulate MSCs to maximize the production of their exosomes carrying therapeutic molecules. My Lab aims to address these questions by investigating the role of metabolism in exosome biogenesis, because multiple steps of exosome biogenesis, including vesicle formation inside a cell and fusing into the plasma membrane, are directly associated with metabolic processes. In this Project, we will investigate how the exosome generation rate and molecular contents are determined under different metabolic conditions, specifically with the modulation of nutrients and NAD levels. We will also develop a single exosome sorting technology based on intravesicular proteins and investigate the biogenesis of exosomes with mitochondrial molecules under mitochondrial stress conditions. The research accomplishments from this Project will deepen our understanding of exosomes and help us develop exosome-based diagnostic and therapeutic strategies more effectively. Our long-term research goal is to identify the mechanisms of the interplay between metabolism and biogenesis of extracellular vesicles (EVs). This MIRA research focuses on exosomes, a subpopulation of EVs. Based on our research progresses, we will expand our research scope to other EVs, including microvesicles, in the future.