Abstract
Visualizing and tracking mitochondrial dynamic changes is crucially important in the fields of physiology, pathology and pharmacology. Traditional electrostatic-attraction based mitochondrial probes fail to visualize and track the changes due to their leakage from mitochondria when mitochondrial membrane potential (MMP) decreases. Reaction-based MitoTracker probes can realize visualization and tracking of mitochondria changes independent of MMP changes. However, such probes impair mitochondrial proteins and exhibit high cytotoxicity. Therefore, it still remains challenging to explore reaction-free and highly biocompatible probes for visualizing and tracking mitochondrial dynamics independent of MMP fluctuations. Herein we synthesized two reaction-free fluorescent mitochondrial probes ECPI-12 and IVPI-12 bearing a long C12-alkyl chain. These cationic probes can firmly immobilize in the mitochondrial inner membrane by strong hydrophobic interaction between the C12-alkyl chain and lipid bilayer, resulting in high specificity and long-term mitochondrial staining regardless of MMP changes. They also exhibit large two-photon absorption cross-sections and show deep penetration in live tissues in two-photon microscopy. Furthermore, they display excellent biocompatibility and realize in situ and real-time mitophagy tracking in live cells. These excellent properties could make ECPI-12 and IVPI-12 the first selective tools for long-term visualization and tracking of mitochondrial dynamics.
Highlights
The dynamic changes of mitochondrial morphology and number are highly relevant to numerous physiological and pathological processes.[1,2] Recent studies have indicated that mitochondrial morphology changes from a tubular network to a punctiform and fragmented formation during the early stage of apoptotic cell death.[3]
By comparing with ECPI-2 and IVPI-2 bearing a short alkyl chain (Scheme 1(2)), we proved that the long-alkyl-chain-induced hydrophobic interaction allows ECPI-12 and IVPI-12 to be retained for a long time in mitochondria when the membrane potential (MMP) decreases or vanishes
We anticipate that a long-lipophilic-aliphatic-chainmodi ed cationic probe could realize long-term retention in mitochondria by the above-mentioned strong hydrophobic interaction, which is probably independent of the in uence of MMP changes (Scheme 1(1C))
Summary
The dynamic changes of mitochondrial morphology and number are highly relevant to numerous physiological and pathological processes.[1,2] Recent studies have indicated that mitochondrial morphology changes from a tubular network to a punctiform and fragmented formation during the early stage of apoptotic cell death.[3]. Ruoyao Zhang,‡ab Guangle Niu, ‡b Xuechen Li,a Lifang Guo,a Huamiao Zhang,a Rui Yang,a Yuncong Chen, b Xiaoqiang Yu *a and Ben Zhong Tang*b
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