Using light to restore cellular function

New research from the University of Cincinnati shows the first indications that light can be used as a treatment for certain diseases, including most cancers.

Researchers from UC, the University of Illinois at Urbana-Champaign and the University at Buffalo have released the results of their study showing that light-activated proteins can help normalize dysfunction within cells in the journal Nature Communications on 25 July.

Research focuses on the functions of mitochondria, organelles within a cell that act as the cell’s “powerhouse” and energy source. Organelles are tiny, specialized structures that perform various tasks inside cells.

Jiajie Diao, PhD, one of the study authors, said that Hundreds of mitochondria are constantly coming together (a process called fusion) and dividing into smaller parts (a process called fission) to stay balanced in healthy cells. But when the mitochondria are not working properly, there is an imbalance of this fission and fusion process.

This imbalance can lead to a number of mitochondrial diseases including neurodegenerative diseases such as dementia and certain cancers.

Diao said that previous research has revealed that another organelle in cells called the lysosome may play a role in the fission of mitochondria. When a mitochondria comes into contact with a lysosome, the lysosome can act like a pair of scissors and cut the mitochondria into smaller pieces.

Current research has focused on starting the fission process by bringing lysosomes and mitochondria closer together within cells. This was accomplished using a technique known as optogenetics, which can precisely control specific cell functions using light.

“Many proteins in plants are light-sensitive, telling plants whether it is day or night. said Kai Zhang, PhD, associate professor at the University of Illinois Urbana-Champaign and co-author of the study, who developed the optogenetic tools to control mitochondria and lysosomes with blue light. “By attaching such proteins to organelles, one can use light to control the interaction between them, like the mitochondria and lysosomes shown in this work,” he said.

Researchers attached two separate proteins to mitochondria and lysosomes in stem cells. When stimulated by blue light, proteins naturally bind together to form a new protein, which also disrupts the mitochondria and lysosome. Once they are reunited, the lysosome can cut the mitochondria, achieving fission.

“We found that it can recover mitochondrial function,” Diao said, associate professor in the Department of Cancer Biology at the UC College of Medicine and member of the University of Cincinnati Cancer Center. “Some of the cells may even go back to normal. This proves that by simply using light stimulation, we can at least partially recover the mitochondrial function of the cell.”

Diao said this technique could be particularly useful for people with significantly oversized mitochondria that need to be broken into smaller pieces to achieve normal cellular function. The system could also target cancer cells, continually tearing mitochondria into smaller and smaller pieces until they can no longer function.

“Eventually, cancer cells will be killed because mitochondria are their energy,” Diao said. “Without normal functioning mitochondria, all cancer cells will be killed.”

Given that proteins are activated by light, Diao said this allows for a more targeted approach to specific cells. Only cells exposed to light are affected, meaning nearby healthy cells do not have their mitochondria unbalanced by the method.

There are currently other processes which can be used to induce mitochondrial fission, but Diao said the optogenetic method is safer because it does not involve any toxic chemicals or agents.

“What we have is actually the natural process, we just make it faster,” Diao said. “So it’s not like a chemical or therapy or radiation therapy where you have to reduce the side effects.”

Next Steps

Diao said his team is already working on using the same procedure to encourage fusion to address issues when mitochondria are out of balance because they are too small and do not congregate in cells as they should. light, including green, red and infrared, as a longer wavelength will be required to penetrate human tissue.

“We would like to expand the box further tools by introducing multicolored optogenetic systems to give us multiple ways to control the behavior and interaction of s organelles,” Zhang said. “For example, one color brings the organelles together, while the other separates them. This way, we can precisely control their interactions.”

Building on current research using human stem cells, the team hopes to progress to test its effectiveness in human models. animals with a view to possibly testing the method in humans through clinical trials. At the same time, Diao said other research groups are studying the use of magnetic fields and acoustic vibrations instead of light to achieve similar results.

This work was supported by the Nationwide Institutes of Wellness (NIH R35GM128837 and R01AG061600 to JD R01GM

and R124827 MH124827 to KZ). The authors declare no competing interests.

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