Lumos! US researchers show how light can be used to treat cancers

It is all about correcting mitochondrial dysfunction.
Ameya Paleja
  • Mitochondria in the cell can fuse and divide as required.
  • Optogenetics allows researchers to control biological functions using a light source.
  • With help of plant proteins, researchers were able to control mitochondria fusion and fission.

A collaboration of researchers from various universities in the U.S. has demonstrated how light-activated proteins could one day be used to treat diseases like cancer, a press release said.

Optogenetics is a relatively new field of science where researchers monitor and control the biological functions in a cell or a tissue using genetic engineering techniques and an optical system. Theoretically, the field has the potential to allow researchers to control your mind, but since real-world researchers are more concerned with solving problems, you are more likely to hear about this technology helping to treat diseases.

When researchers at the University of Cincinnati, the University of Illinois Urbana-Champaign, and the University at Buffalo came together, they decided to utilize the technology to focus on the diseases caused by dysfunctioning mitochondria.

What diseases can mitochondria cause?

Mitochondria are cell organelles present inside the cell which produce energy needed to carry out cellular functions. As the powerhouse of the cell, the role of mitochondria is very important. The cell has them in abundant numbers and can even fuse or split them apart depending on its requirements.

Hundreds of mitochondria can come together and form one large organelle through the process called fusion. When needed, these organelles can also divide further into smaller parts in a process called fission and maintain a healthy balance inside the cell.

When mitochondria are dysfunctional, the processes of fusion and fission are also affected, and this can lead to diseases like dementia and cancer, where the mitochondria numbers have been found to be far from normal. Recently, we reported another study where researchers treated a lethal type of cancer by restoring the number of mitochondria in the tumorous cells.

What role does optogenetics play?

Previous research has shown that another cell organelle called lysosome aids the process of fission of mitochondria. When a lysosome comes in contact with mitochondria, it acts like a pair of scissors and splits them.

The researchers used light-sensitive proteins that are found in plants and attached them to organelles in an animal cell. Since these proteins respond to light, they can be used to control the interaction between the organelles as well.

In this case, the researchers used two separate plant proteins and attached them to mitochondria and lysosomes in stem cells. Using blue light, the plant proteins were activated and made to bind to each other to form a new protein. While this occurred, the lysosome came in contact with the mitochondria and cut them, achieving the process of fission.

This could be useful in conditions where mitochondria have fused onto one large organelle, and their numbers need to be restored in the cell. Since the process is activated by light, specific cells can be targeted without impacting healthy cells in the neighborhood. Currently, mitochondrial fission is achieved using other processes that require the use of toxic agents and chemicals.

For cancerous cells, the researchers can continue chopping off the mitochondria till there is nothing left to produce energy for the cells.

The research team is also working on ways to use the same technique to achieve the fusion process. Efforts are also underway to use lights of different colors, such as green and red, as well as infrared, which will be needed to penetrate human tissue. "One color makes organelles come together, while the other color forces them apart. This way, we can precisely control their interactions,” said Kai Zhang, associate professor at the University of Illinois Urbana-Champaign.

The findings from the study were published in Nature Communications.

Abstract

Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria–lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46−/− cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.

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