# Optogenetically engineered calcium oscillations promote autophagy-mediated cell death via AMPK activation

## TL;DR

This study shows that high-frequency calcium oscillations, controlled using optogenetics, can trigger cell death through autophagy and AMPK activation.

## Contribution

The novel use of optogenetics to manipulate calcium oscillations and demonstrate their role in AMPK-mediated autophagy-induced cell death.

## Key findings

- High-frequency Ca2+ oscillations induce autophagy and lead to cell death.
- AMP-activated protein kinase is involved in autophagy triggered by Ca2+ oscillations.
- Optogenetic tools allow precise control of Ca2+ influx patterns to study cellular responses.

## Abstract

Autophagy is a double-edged sword for cells; it can lead to both cell survival
and death. Calcium (Ca2+) signalling plays a crucial role in
regulating various cellular behaviours, including cell migration, proliferation
and death. In this study, we investigated the effects of modulating cytosolic
Ca2+ levels on autophagy using chemical and optogenetic methods.
Our findings revealed that ionomycin and thapsigargin induce Ca2+
influx to promote autophagy, whereas the Ca2+ chelator BAPTA-AM
induces Ca2+ depletion and inhibits autophagy. Furthermore, the
optogenetic platform allows the manipulation of illumination parameters,
including density, frequency, duty cycle and duration, to create different
patterns of Ca2+ oscillations. We used the optogenetic tool
Ca2+-translocating channelrhodopsin, which is activated and
opened by 470 nm blue light to induce Ca2+ influx. These results
demonstrated that high-frequency Ca2+ oscillations induce autophagy.
In addition, autophagy induction may involve Ca2+-activated adenosine
monophosphate (AMP)-activated protein kinases. In conclusion, high-frequency
optogenetic Ca2+ oscillations led to cell death mediated by
AMP-activated protein kinase-induced autophagy.