Two-photon and dual-color visualization of Aβ1-40 induced mitophagy by the detection of mitochondrial DNA G-quadruplex and polarity

Mitophagy, as an important process for maintaining mitochondrial function, plays a critical role in the pathogenesis of Alzheimer's disease (AD). The relationship between mitophagy and amyloid β-peptides (Aβ), whose accumulation is a main pathological feature of AD, still remains to be deciphered deeply. Herein, we developed a two-photon fluorescent probe, named Mito-FG, which can specifically bind to mitochondrial DNA G-quadruplex (mtDNA G4) and sensitively detect mitochondrial polarity simultaneously in crosstalk-free two channels. Probe Mito-FG exhibited good two-photon absorption performance, biocompatibility and mitochondria-targeted ability. Through two-photon imaging, we employed Mito-FG to visualize mitophagy through monitoring the changes of mtDNA G4s and mitochondrial polarity in real-time. Moreover, our findings revealed that Aβ1-40 can trigger mitophagy in mouse brain vascular pericytes (MBVP) cells, which was accompanied with the structural damage of mtDNA G4s and a concurrent reduction in mitochondrial polarity. And the results highlighted that Mdivi-1, a neuroprotective drug, can effectively inhibit Aβ1-40-induced mitophagy. Thus, probe Mito-FG is a promising imaging tool for studying the pathological role of Aβ1-40-induced mitophagy in AD as well as screening and evaluating of drugs for AD treatment.