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Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
Light-Up Mitophagy in Live Cells with Dual-Functional Theranostic Phosphorescent Iridium(III) Complexes
Mu-He Chen1, Fang-Xin Wang1, Jian-Jun Cao1
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University , Guangzhou 510275, P. R. China.
Abstract:
Phosphorescent Ir(III) complexes are expected to be new multifunctional theranostic platforms that enable the integration of imaging capabilities and anticancer properties. Mitophagy is an important selective autophagic process that degrades dysfunctional mitochondria. Until now, the regulation of mitophagy is still poorly understood. Herein, we present two phosphorescent cyclometalated iridium(III) complexes (Ir1 and Ir2) that can accumulate in mitochondria and induce mitophagy. Because of their intrinsic phosphorescence, they can specially image mitochondria and track mitochondrial morphological alterations. Mechanism studies show that Ir1 and Ir2 induce mitophagy by depolarization of mitochondrial membrane potential, depletion of cellular ATP, perturbation in mitochondrial metabolic status, and induction of oxidative stress. Moreover, no sign of apoptosis is observed in Ir1- and Ir2-treated cells under the same conditions that an obvious mitophagic response is initiated. We demonstrate that Ir1 is a promising theranostic agent that can induce mitophagy and visualize changes in mitochondrial morphology simultaneously.
Insights
Two novel iridium(III) complexes (Ir1 and Ir2) effectively image mitochondria and induce mitophagy, a key cellular process. This demonstrates their potential as theranostic agents for cancer therapy and diagnostics.
Area of Science:
- Biochemistry
- Cell Biology
- Materials Science
Background:
- Mitophagy, the selective degradation of dysfunctional mitochondria, is crucial for cellular health but its regulation remains unclear.
- Phosphorescent iridium(III) complexes offer potential as theranostic agents, combining imaging and therapeutic capabilities.
- Mitochondria are key targets for cancer therapy due to their role in cellular energy and proliferation.
Purpose of the Study:
- To develop and characterize novel phosphorescent iridium(III) complexes for theranostic applications.
- To investigate the ability of these complexes to induce and image mitophagy.
- To elucidate the underlying mechanisms by which the complexes affect mitochondrial function.
Main Methods:
- Synthesis and characterization of two phosphorescent cyclometalated iridium(III) complexes (Ir1 and Ir2).
- Cellular uptake studies to confirm mitochondrial accumulation.
- Mitochondrial membrane potential, ATP levels, metabolic status, and oxidative stress assays.
- Confocal microscopy for imaging mitochondrial morphology and mitophagy.
- Apoptosis assays to assess cellular toxicity.
Main Results:
- Ir1 and Ir2 efficiently accumulate in mitochondria and exhibit intrinsic phosphorescence for imaging.
- Treatment with Ir1 and Ir2 induced mitophagy, evidenced by mitochondrial depolarization, ATP depletion, metabolic perturbation, and oxidative stress.
- No apoptosis was observed in treated cells, indicating a selective induction of mitophagy.
- Mitochondrial morphological changes were visualized in real-time using the phosphorescent properties of the complexes.
Conclusions:
- Phosphorescent iridium(III) complexes (Ir1 and Ir2) are effective theranostic agents capable of inducing mitophagy.
- These complexes enable simultaneous imaging of mitochondria and tracking of mitophagy-induced morphological alterations.
- Ir1 shows promise as a theranostic platform for cancer treatment, leveraging mitophagy induction and real-time mitochondrial visualization.
