Ca²⁺ as an essential signaling molecule controlling Snf1-mediated Atg1 activation

Abstract

Macroautophagy/autophagy is essential for maintaining glucose homeostasis, but the mechanisms by which cells sense glucose starvation and initiate autophagy are not yet fully understood. Recently, we reported that the assembly of a Ca²⁺-triggered Snf1-Bmh1/Bmh2-Atg11 complex initiates autophagy in response to glucose starvation. Our research reveals that during glucose starvation, the efflux of vacuolar Ca²⁺ increases cytoplasmic Ca²⁺ levels, which activates the protein kinase Rck2. Rck2-mediated phosphorylation of Atg11 enhances its interaction with Bmh1 and Bmh2. This interaction recruits the Snf1-Sip1-Snf4 complex, which is located on the vacuolar membrane, to the phagophore assembly site (PAS), leading to the activation of Atg1 and the initiation of autophagy. In summary, we have identified a previously unrecognized signaling pathway involved in glucose starvation-induced autophagy, where Ca²⁺ acts as a fundamental signaling molecule that links energy stress to the formation of the autophagy initiation complex.

Keywords:

• Atg11-Bmh1/2-Snf1 complex
• autophagy
• Ca²⁺
• glucose starvation
• Rck2

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Acknowledgements

The research was supported by the National Natural Science Foundation of China (Grant Nos. 32122028, 92254307, and 32070739) awarded to Cong Yi, and the National Natural Science Foundation of China (Grant Nos. 31601125 and 32072334) awarded to Yanyang Wu.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [31601125, 32072334]; National Natural Science Foundation of China [32122028, 92254307, and 32070739].