Determination of mitochondrial lipid packing in healthy and cancerous cell lines

健康细胞系和癌细胞系中线粒体脂质堆积的测定

• 批准号: 580248-2022
• 负责人: Marquardt, DrewTC
• 金额: $ 1.82万
• 依托单位: University of Windsor
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748408
• 关键词: Determination; mitochondrial; lipid; packing; healthy

Regulation of mitochondrial apoptosis is essential for physiological development and tissue health inmammalian cells. Diverging from programmed cell death can lead to an array of complications including, but not limited to, cancer. However, this apoptotic mechanism can be exploited to specifically target the mitochondria of cancerous cells, while leaving surrounding healthy cells unscathed. Conventional cancer treatments use highly cytotoxic agents in combination with radiation therapy that act on both cancerous and non-cancerous cells eliminating or reducing tumor growth. Unfortunately, these traditional methods and drugs (e.g., DNA intercalating agents) are genotoxic and have the potential to lead to the manifestation of additional cancers later in life. Thus, a fundamental understanding of similarities and differences in mitochondria can provide health researchers the necessary foundation to develop more effective anti-cancer agents.We propose to use very small angle neutron scattering (vSANS) to compare the mitochondrial structure of healthy and cancerous mitochondria from multiple cell types. vSANS offers many advantages for the study of biological systems as neutron scattering is sensitive to light elements commonly found in lipids in biological membranes. Further, the use of vSANS will allow for the direct observation of mitochondria from the molecular organization to their full size (2 microns) in their native aqueous environment.This project will answer key questions about composition and structural differences between healthy andcancer cells ultimately stimulating a new application and research avenue for SANS to shed light on themechanism of cancer therapeutics.

线粒体凋亡的调控对哺乳动物细胞的生理发育和组织健康至关重要。偏离程序性细胞死亡可能导致一系列并发症，包括但不限于癌症。然而，这种凋亡机制可以被利用来特异性地靶向癌细胞的线粒体，同时使周围的健康细胞毫发无损。常规癌症治疗使用高细胞毒性剂与放射疗法组合，其作用于癌细胞和非癌细胞两者，消除或减少肿瘤生长。不幸的是，这些传统的方法和药物（例如，DNA嵌入剂）具有遗传毒性，并有可能导致生命后期出现其他癌症。因此，线粒体的相似性和差异的基本理解，可以提供健康研究人员开发更有效的抗癌agents.We建议使用非常小角中子散射（vSANS）比较健康和癌线粒体的线粒体结构从多种细胞类型的必要基础。vSANS为生物系统的研究提供了许多优势，因为中子散射对生物膜中脂质中常见的轻元素敏感。此外，vSANS的使用将允许直接观察线粒体从分子组织到其天然水环境中的完整尺寸（2微米）。该项目将回答有关健康细胞和癌细胞之间的组成和结构差异的关键问题，最终激发SANS的新应用和研究途径，以阐明癌症治疗的机制。