A DNA-Based FLIM Reporter for Simultaneous Quantification of Lysosomal pH and Ca2+ during Autophagy Regulation

IScience
Zhonghui ZhangYang Tian

Abstract

pH and Ca2+ play important roles in regulating lysosomal activity and lysosome-mediated physiological and pathological processes. However, effective methods for simultaneous determination of pH and Ca2+ is the bottleneck. Herein, a single DNA-based FLIM reporter was developed for real-time imaging and simultaneous quantification of pH and Ca2+ in lysosomes with high affinity, in which a specific probe for recognition of Ca2+ was assembled onto a DNA nanostructure together with pH-responsive and lysosome-targeted molecules. The developed DNA reporter showed excellent biocompatibility and long-term stability up to ∼56 h in lysosomes. Using this powerful tool, it was discovered that pH was closely related to Ca2+ concentration in lysosome, whereas autophagy can be regulated by lysosomal pH and Ca2+. Furthermore, Aβ-induced neuronal death resulted from autophagy abnormal through lysosomal pH and Ca2+ changes. In addition, lysosomal pH and Ca2+ were found to regulate the transformation of NSCs, resulting in Rapamycin-induced antiaging.

References

Mar 1, 1990·Trends in Pharmacological Sciences·D Rampe, D J Triggle
Mar 18, 2005·Journal of the American Chemical Society·Masanori SakamotoTetsuro Majima
Oct 22, 2005·Nature Reviews. Cancer·Guido Kroemer, Marja Jäättelä
May 16, 2007·Journal of the American Chemical Society·Christoph M ErbenAndrew J Turberfield
Jul 20, 2007·Nature Reviews. Molecular Cell Biology·J Paul LuzioNicholas A Bright
Jul 29, 2010·PLoS Genetics·Vikram KhuranaMel B Feany
Sep 3, 2010·Nature Cell Biology·Zhifen Yang, Daniel J Klionsky
Sep 28, 2010·Chemical Society Reviews·Shiping SongHong-Yuan Chen
Sep 3, 2011·Cell·David C RubinszteinGuido Kroemer
Apr 24, 2013·Nature Reviews. Molecular Cell Biology·Carmine SettembreAndrea Ballabio
Aug 10, 2016·Science China. Life Sciences·Michael X ZhuJenny J Yang
Apr 25, 2018·Nature Chemical Biology·Daria M ShcherbakovaLouis Hodgson
Jan 19, 2001·Angewandte Chemie·Peng ZhangWeihong Tan
Jun 6, 2018·Nature Chemical Biology·Jianchao LiMingjie Zhang
Aug 8, 2018·Nature Nanotechnology·Yong FanFan Zhang
Oct 27, 2018·Analytical Chemistry·Pieter E OomenAndrew G Ewing
Nov 7, 2018·Nature Chemical Biology·Huanbin WangJie Xu
Dec 5, 2018·Nature Nanotechnology·KaHo LeungYamuna Krishnan
Dec 12, 2018·Nature Methods·Nagarjun NarayanaswamyYamuna Krishnan
Jun 22, 2019·Nature Chemical Biology·Luca LaraiaHerbert Waldmann
Jul 10, 2019·Nature Chemical Biology·Clive Yik-Sham ChungDaniel K Nomura
Aug 1, 2019·Chemical Communications : Chem Comm·Zhichao LiuYang Tian

❮ Previous
Next ❯

Methods Mentioned

BETA
biosensing
electrophoresis
transmission electron microscopy
AFM
dynamic light scattering
Fluorescence
fluorescence-activated cell sorting
FACS
FRET

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms