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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Open biology - 14(2024), 4 vom: 23. Apr., Seite 240001

Sprache:

Englisch

Beteiligte Personen:

Lai, Yi-Shyun [VerfasserIn]
Hsieh, Meng-Ru [VerfasserIn]
Nguyen, Thi My Hang [VerfasserIn]
Chen, Ying-Chi [VerfasserIn]
Wang, Hsueh-Chun [VerfasserIn]
Chiu, Wen-Tai [VerfasserIn]

Links:

Volltext

Themen:

56092-81-0
67526-95-8
AMP-Activated Protein Kinases
AMPK
Autophagy
Calcium
Cell death
EC 2.7.11.31
Ionomycin
Journal Article
Optogenetics
Research Support, Non-U.S. Gov't
SY7Q814VUP
Thapsigargin

Anmerkungen:

Date Completed 24.04.2024

Date Revised 01.05.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1098/rsob.240001

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM37142237X