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Review
. 2015;11(6):970-1.
doi: 10.1080/15548627.2015.1047130.

Lysosomal calcium regulates autophagy

Diego L Medina  1 , Andrea Ballabio
Affiliations
Review

Lysosomal calcium regulates autophagy

Diego L Medina et al. Autophagy. 2015.

Abstract

Recent evidence has indicated that the lysosome is able to act as a signaling organelle that senses nutrient availability and generates an adaptive response that is important for cellular homeostasis. We recently discovered another example of lysosomal signaling where lysosomal calcium release activates the master autophagy regulator TFEB via the phosphatase calcineurin.

Keywords: TFEB; TRPML1; autophagy; calcineurin; lysosomal calcium.

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Figures

Figure 1.
Figure 1.
Model of TFEB regulation by lysosomal calcium. In nutrient-rich conditions TFEB is phosphorylated by MTOR in the lysosome and sequestered in the cytoplasm by interacting with YWHAB/14-3-3 proteins. During starvation or physical exercise, calcium is released from the lysosome via MCOLN1 leading to local calcineurin (CaN) activation and TFEB dephosphorylation. Dephosphorylated TFEB can shuttle to the nucleus where it transcriptionally activates the lysosomal/autophagic pathway.
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