Insights into mitochondria-lysosome contact dynamics in neurodegeneration

深入了解神经退行性变中的线粒体-溶酶体接触动力学

• 批准号: 10403821
• 负责人: Yvette Wong
• 金额: $ 3.11万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10403821
• 关键词: Automobile Driving; Disease; Etiology; Functional disorder; Health; Homeostasis; Lysosomes; Membrane; Microscopy; Mitochondria; Nerve Degeneration; Neurodegenerative Disorders; Organelles; Pathogenesis; Pathway interactions; Regulation; Research; Research Project Grants; Role; Site; Time; insight; nervous system disorder

PROJECT SUMMARY Both mitochondria and lysosomes are critical for health and homeostasis, and dysfunction of both organelles has been implicated in multiple neurodegenerative diseases. However, the crosstalk between these two organelles in driving disease pathogenesis is still not well understood. Inter-organelle membrane contacts form between different organelles and are critical sites for modulating organelle dynamics and function. Mitochondria and lysosomes can form such inter-organelle contact sites, and their crosstalk at mitochondria- lysosome contacts represents a key pathway for the bidirectional regulation of mitochondria and lysosomes. Importantly, further studying the role of mitochondria-lysosome contacts may provide important insights into the regulation of mitochondrial and lysosomal function, and their contribution to the etiology of different neurological disorders. This research project will investigate the role of mitochondria-lysosome contact site misregulation in specific neurodegenerative diseases using advanced time-lapse microscopy. Ultimately, the proposed research will help uncover new mechanisms underlying disease pathogenesis at the intersection of inter-organelle contact sites and neurodegeneration.

项目摘要 线粒体和溶酶体对健康和体内平衡以及两种细胞器的功能障碍都至关重要 与多种神经退行性疾病有关然而，这两者之间的串扰 细胞器在驱动疾病发病机制中的作用仍然没有得到很好的理解。细胞器间膜接触形式 在不同的细胞器之间，并且是调节细胞器动力学和功能的关键位点。 线粒体和溶酶体可以形成这样的细胞器间接触位点，它们在线粒体- 溶酶体接触代表了线粒体和溶酶体双向调节的关键途径。 重要的是，进一步研究溶酶体接触的作用可能会对细胞的增殖提供重要的见解。 线粒体和溶酶体功能的调节，以及它们对不同病因学的贡献 神经系统疾病本研究计划将探讨大肠杆菌-溶酶体接触位点的作用 使用先进的延时显微镜在特定的神经退行性疾病中的失调。最终 拟议的研究将有助于揭示疾病发病机制的新机制， 细胞器间接触部位和神经变性。