A Continuous Add-On Probe Reveals the Nonlinear Enlargement of Mitochondria in Light-Activated Oncosis
Kang-Nan Wang1, Xintian Shao2,3,4, Zhiqi Tian5
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.
Abstract:
Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior of mitochondria during oncosis, due to the lack of probes for in situ visual illumination of the mitochondrial membrane and mtDNA. Herein, a mitochondrial lipid and mtDNA dual-labeled probe, MitoMN, and a continuous add-on assay, are designed to image the dynamic process of mitochondria in conditions that are unobservable with current mitochondrial probes. Meanwhile, the MitoMN can induce oncosis in a light-activated manner, which results in the enlargement of mitochondria and the death of cancer cells. Using structured illumination microscopy (SIM), MitoMN-stained mitochondria with a dual-color response reveals, for the first time, how swelled mitochondria interacts and fuses with each other for a nonlinear enlargement to accelerate oncosis into an irreversible stage. With this sign of irreversible oncosis revealed by MitoMN, oncosis can be segregated into three stages, including before oncosis, initial oncosis, and accelerated oncosis.
Insights
Researchers developed MitoMN, a novel probe to visualize mitochondria during oncosis. This allows observation of mitochondrial swelling and fusion, revealing new insights into cancer cell death mechanisms and enabling staged classification of oncosis.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Oncosis is a crucial cancer treatment strategy involving DNA damage and mitochondrial swelling.
- Current limitations in visualizing mitochondrial behavior and mtDNA during oncosis hinder understanding.
- Lack of specific probes restricts in situ observation of mitochondrial dynamics.
Purpose of the Study:
- To develop a dual-labeled probe (MitoMN) for simultaneous imaging of mitochondrial lipids and mtDNA.
- To investigate mitochondrial dynamics and their role in oncosis progression.
- To establish a method for light-activated induction and observation of oncosis.
Main Methods:
- Design and synthesis of MitoMN, a mitochondrial lipid and mtDNA dual-labeled probe.
- Development of a continuous add-on assay for dynamic imaging.
- Application of structured illumination microscopy (SIM) for high-resolution visualization.
- Light-activated induction of oncosis in cancer cells.
Main Results:
- MitoMN successfully imaged mitochondrial membrane and mtDNA dynamics during oncosis.
- MitoMN demonstrated light-activated induction of oncosis, leading to mitochondrial enlargement and cancer cell death.
- SIM imaging revealed mitochondrial fusion and nonlinear enlargement, accelerating oncosis.
- Oncosis was successfully classified into three distinct stages: pre-oncosis, initial oncosis, and accelerated oncosis.
Conclusions:
- MitoMN provides unprecedented insights into mitochondrial behavior during oncosis.
- The study elucidates the mechanism of mitochondrial swelling and fusion in accelerating oncosis.
- This work enables a new, staged understanding of oncosis progression, crucial for cancer therapy development.
