Construction of fluorescent probes for ratiometric visualization of mitochondrial depolarization based on the FRET mechanism

Abstract

Mitochondria supply the majority of energy to sustain the biological activities in living cells, and mitochondrial dysfunction would lead to serious diseases. Mitochondrial depolarization is a sign of mitochondrial dysfunction, which can indicate the health status of both mitochondrial and living cells. Thus, visualizing mitochondrial depolarization is a tough yet crucial task in the biomedical area. In this work, fluorescent probes that enable the visualization of mitochondrial depolarization in a ratiometric manner have been fabricated based on the Förster resonance energy transfer (FRET) mechanism. Both the FRET donor and acceptor were modified with cationic groups and target mitochondria in living cells. Further, the donor and acceptor probes were designed to exhibit no and certain affinity to RNA, respectively. As a result, the FRET donor and acceptor targeted mitochondria in living cells, exhibiting weak blue and strong red emissions owing to the FRET process. After mitochondrial depolarization, the donor and acceptor targeted membranous organelles and RNA, respectively. The FRET process was inhibited, and only blue emission was detected. Thereby the mitochondrial depolarization could be visualized in a ratiometric manner.