# Optogenetic engineering of BAX to control mitochondrial permeabilization and attenuate apoptosis in cells

## TL;DR

Scientists used light to control a protein called BAX, which is involved in cell death, offering a new way to study and treat diseases like Alzheimer's.

## Contribution

A novel optogenetic approach to modulate BAX activity and inhibit apoptosis with precise spatial control.

## Key findings

- Engineered BAX variant is effectively incapacitated in its apoptotic function.
- Modified BAX enhances cellular resistance to apoptosis by preventing mitochondrial pore formation.
- Optogenetic control of BAX provides a tunable strategy for antiapoptosis.

## Abstract

Although considerable research has focused on enhancing the apoptotic function of BAX for several decades, inhibition of its functionality remains relatively underexplored, despite intensive BAX activation occurring in various neurodegenerative diseases. Here we present a protein engineering approach to modulate BAX integration into the mitochondrial outer membrane, establishing a tunable strategy for antiapoptosis. Utilizing optogenetic methods that employ cryptochrome 2 and its binding partner cryptochrome-interacting basic helix loop helix 1, we achieved precise spatial control over BAX localization, a critical determinant of its function. Our results demonstrate that the engineered BAX variant is effectively incapacitated in its apoptotic function while also modulating endogenous BAX activity to enhance cellular resistance to apoptosis. These findings not only advance our understanding of BAX regulation but also offer promising prospects for the development of therapeutic strategies against apoptosis-related diseases.

BAX is a protein that helps control cell death, which is important for removing damaged or harmful cells. However, when this process goes wrong, it can lead to diseases such as cancer or Alzheimer’s disease. Researchers explored a new way to control BAX using light to better understand and potentially treat these conditions. The study used optogenetics to precisely manipulate BAX in cells. They created a modified version of BAX that can be controlled with blue light, allowing them to study its effects on cell death. This approach helps avoid unintended side effects common with other methods. Researchers found that their modified BAX could reduce cell death by preventing BAX from forming pores in the cell’s mitochondria. This discovery suggests that controlling BAX with light could be a promising strategy for treating diseases.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.