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Intracellular calcium signaling regulates autophagy via calcineurin-mediated TFEB dephosphorylation

Yanju Tong1, Fuyong Song

  • 1a Department of Toxicology; School of Public Health; Shandong University ; Jinan , Shandong , China.

Autophagy
|June 6, 2015
PubMed

Insights

The study identifies calcineurin as the key phosphatase that dephosphorylates transcription factor EB (TFEB). This dephosphorylation, triggered by lysosomal calcium signaling, upregulates autophagy, a crucial cellular process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Transcription factor EB (TFEB) regulates cellular functions through its transcriptional activity.
  • TFEB's activity is modulated by phosphorylation, but the phosphatases responsible for its dephosphorylation were unknown.
  • Autophagy is a vital cellular process for maintaining homeostasis.

Purpose of the Study:

  • To identify the phosphatase responsible for TFEB dephosphorylation.
  • To elucidate the signaling pathway linking lysosomal calcium to TFEB activity and autophagy.

Main Methods:

  • Investigated the role of calcineurin in TFEB dephosphorylation using biochemical assays.
  • Utilized cell-based models to study the effects of lysosomal calcium signaling on TFEB and autophagy.

Main Results:

  • Lysosomal calcium signaling activates calcineurin, a serine/threonine phosphatase.
  • Calcineurin directly dephosphorylates TFEB.
  • Dephosphorylation of TFEB by calcineurin leads to the upregulation of autophagy.

Conclusions:

  • Calcineurin is the primary phosphatase mediating TFEB dephosphorylation.
  • Lysosomal calcium-activated calcineurin is a key regulator of TFEB-driven autophagy.
  • This finding reveals a novel mechanism controlling autophagy.
Keywords:
calcineurincalcium signalingtranscription factor EB

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