University of Cincinnati College of Medicine

报告摘要：

Mitochondria–lysosome interactions including contact (MLC) and fusion (mitophagy) are essential for maintaining intracellular homeostasis. Defective mitochondria-lysosome interactions often associate with neurodegenerative diseases and cancer. Mitochondria and lysosomes form dynamic inter-organelle membrane contact sites, mediate inter-organelle transfer of metabolites, and contribute to the pathogenesis in diseases linked to dysfunction of both organelles. Although various fluorescent probes have been developed for visualization of mitochondria–lysosome interaction, they lack the capacity of simultaneous labeling of mitochondria and lysosomes and dynamic tracking of their interaction.

Herein, we introduce a cellular permeable, biocompatible, viscosity-responsive small organic molecular probe, Coupa, to stain mitochondria and lysosomes simultaneously and monitor the interaction of mitochondria and lysosomes in living cells. Under normal physiological conditions, Coupa attaches to lysosomes and emits red fluorescence (Coupa-lyso). When exposed to reactive sulfur species in mitochondria, Coupa is biomodified into a new compound that emits blue fluorescence (Coupa-mito). Using structured illumination microscopy, we showed that Coupa dyes are capable to report the functional interactions of mitochondria and lysosomes in mitophagy process through co-localization and correlated fluorescence change. Dual-color labeling of Coupa dyes induced by functional fluorescence conversion can avoid false position induced by co-localization of two traditional dyes only. Moreover, we demonstrated that the viscosity-sensitive Coupa precisely localizes the MLC sites through reporting local viscosity change on mitochondria. With good cell permeability, non-toxicity, and excellent photobleaching resistance, Coupa could lead to new insights into the dynamic nature of mitochondria-lysosome interactions in living cells.

报告人简介：

刁佳杰，现任美国辛辛那提大学医学院助理教授。2010年博士毕业于伊利诺伊大学物理系，师从美国科学院院士Taekjip Ha教授。2011年1月至2012年10月，在斯坦福大学医学院及霍华德休斯医学研究所从事博士后研究工作，师从美国科学院院士Axel T.Brunger教授；自2012年7月起，晋升为长期职位的霍华德休斯医学研究所研究专员。2012年10月至2015年10月，在西安交通大学生命科学与技术学院前沿研究院担任研究小组主任。2015年10月至今，就职于美国辛辛那提大学医学院助理教授。 论文发表：超过50篇论文发表于国际权威期刊，其中包括Nature（3篇），Nat Struct Mol Biol，Nat Commun，Nat Protoc（2篇），PNAS（5篇），Elife（3篇），EMBO J，JACS，Biomaterials，获得了超过1000 次引用。

联系人：陆颖 (82648122, yinglu@iphy.ac.cn)

本次活动由中科院物理所青促会小组主办