Revealing the Mitochondrial Oxidative Damage Process Using Real-Time Cell Environment Detection Materials

UNIST Researchers Develop Multifunctional Material Capable of Inducing Mitochondrial Oxidative Damage and Detecting Microenvironment

Expected to Improve Oxidation-Based Photodynamic and Radiation Therapy for Cancer Cells … Published in Nature Commu

A research figure presenting mitochondrial morphological changes and cell death mechanisms using the developed substance.

[Asia Economy Yeongnam Reporting Headquarters Reporter Kim Yong-woo] Domestic researchers have revealed the oxidative damage pathway of mitochondria using a substance that detects intracellular microenvironmental changes in real time.

This study is expected to greatly contribute to the advancement of cancer treatment technologies such as photodynamic therapy (PDT) and radiation therapy, which artificially induce oxidative damage in cancer cells.

The research team led by Professors Kwon Tae-hyuk and Seo Jeong-gon at Ulsan National Institute of Science and Technology (UNIST, President Lee Yong-hoon) developed a multifunctional organometallic molecule that oxidatively damages mitochondria while sensing changes in the surrounding environment.

This molecule is designed to absorb external light to generate reactive oxygen species and emit new light containing information such as viscosity and polarity around the mitochondria.

The researchers combined the developed technology with protein analysis techniques to propose the pathway by which mitochondrial oxidation leads to cell death.

Mitochondria are essential intracellular organelles that produce the energy cells need. The oxidation of mitochondria by reactive oxygen species is applied in various cancer treatment medical industries and is known to be highly related to neurodegenerative diseases and heart diseases.

However, the specific mechanism by which mitochondrial oxidation causes functional decline or ultimately leads to cell death has not yet been elucidated.

The research team proposed a mechanism in which specific protein denaturation in mitochondria increases the viscosity of the mitochondrial membrane, induces depolarization, and causes cell death.

The increase in viscosity and depolarization causes material transport obstruction, swelling the mitochondria and interfering with their normal function.

According to the study, when the developed substance is injected into cancer cells, it selectively attaches only to the mitochondrial membrane of the cells. When exposed to a very small amount of light energy (0.1 J/cm2), equivalent to about one second of sunlight on a clear day, sufficient reactive oxygen species are generated to induce cancer cell death.

Additionally, by analyzing the energy transfer phenomenon between the side branches (functional groups) of this substance, information about the polarity and viscosity around the mitochondria can be obtained, as the energy transfer appears in the form of light.

Professor Kwon Tae-hyuk of UNIST (center front row) and researchers.

Professor Seonggon Seo, UNIST.

Lee Chae-heon, a joint first author and integrated master's and doctoral course researcher in the Department of Chemistry at UNIST, explained, “Thanks to analyzing the lifetime and wavelength of the light (luminescence) emitted by the developed organometallic complex, we were able to obtain information on membrane viscosity and polarity, allowing us to accurately understand the mitochondrial oxidative damage process.”

Nam Jeong-seung, also a joint first author and integrated master's and doctoral course researcher in the Department of Chemistry at UNIST, said, “Proteomics-based protein analysis supported the cell death mechanism caused by mitochondrial oxidation. This study is an achievement of interdisciplinary research between chemistry and biology.”

The research team also discovered through morphology change detection that when mitochondria are oxidized, the phenomena of mitochondria splitting or fusing occur more frequently.

Professor Kwon said, “The developed substance effectively kills cancer cells while showing the precise process by which mitochondrial oxidation leads to cell death. It is expected to contribute to the advancement of oxidative stress-based anticancer therapies, including photodynamic therapy.”

This study was published online on January 4 in the international journal Nature Communications. The research was supported by the National Research Foundation of Korea (NRF), Korea Institute of Energy Technology Evaluation and Planning (KETEP), Asan Foundation Biomedical Science Scholarship Program, Global Ph.D. Fellowship Program (GPF), and Ulsan National Institute of Science and Technology (UNIST).

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