Mitochondria play an important role in key biological processes, and mitochondrial dysregulation has been linked to a variety of diseases. Therefore, chemical tools to study mitochondrial function and dynamic processes are essential for understanding intracellular chemical biology. Previous methods have focused on long-term live-cell compatible probes and super-resolution dyes, but the specific characterization of specific subcellular structures is still limited.
Recently,Department of Chemical and Biomolecular Engineering, National University of SingaporeGuillermoBazinTeam of professorsA novel conjugated oligoelectrolyte COE-CN was constructed to enable real-time monitoring of mitochondrial damage, thereby providing a new tool for the study of cell function and drug targets. The study, titled "Real-time Monitoring of Mitochondrial Damage Using Conjugatedoligoelectrolytes," was published in the Journal of the American Chemical Society.
Membrane intercalated conjugated oligoelectrolytes (MICOEs) are a class of molecules with optically active conjugated nuclei flanked by ionic overhang groups. Lipid bilayer mimic distribution of hydrophobic and hydrophilic domains promotes spontaneous membrane intercalation and environment-specific fluorescence emission. These features distinguish COEs from optical reporter proteins that are associated with other specific targets or anchored to the lipid bilayer by hydrophobic domains. The biocompatible, physicochemical, and photophysical properties of micoes allow for biological applications, including labeling or killing microorganisms, tracking extracellular vesicles, and cell imaging. Despite these applications, little is known about the molecular signatures that influence the interaction of COEs with mammalian cells, especially within subcellular organelles. In the case of CoE-S6, a typical cationic oligostyrene (Oligo-PV) CoE, previous colocalization studies have shown no mitochondrial association, instead, it is fully localized in lysosomes upon cellular internalization, as shown in Figure 1.
Figure 1Intracellular accumulation of COE-CN (mitochondria), COE-S6 (lysosomes) and COE-BO (lysosomes) and their chemical structures.
In summary, the authors constructed a new COE derivative, COE-CN, which can be rapidly localized within the microchondria without staying on the plasma membrane. This specificity differs from previous generations of COEs, which predominantly pass the endocytic pathway chromatin membrane or intracellular vesicles, and are independent of the target motif. COE-CN enables selective visualization of mitochondria with brightness and photostability suitable for practical applications. In addition, its membrane potential-dependent accumulation enables the use of COE-CN to identify mitochondrally damaged cells, thus providing a new, simple, and relevant optical reporter cell for rapid screening of mitochondrial dysfunction. The combination of COE-CN with a prolonged MICOE that was found to be dislocated after ** makes mitochondrial health assessment possible. More broadly, based on these findings, the authors expect to develop new COE molecular designs as targetable intracellular optical probes capable of monitoring specific cellular parameters relevant to disease recognition.
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