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Review
. 2016 Oct 6:32:255-278.
doi: 10.1146/annurev-cellbio-111315-125407. Epub 2016 Jun 1.

TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress

Nina Raben  1 , Rosa Puertollano  2
Affiliations
Review

TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress

Nina Raben et al. Annu Rev Cell Dev Biol. .

Abstract

In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases.

Keywords: TFE3; TFEB; autophagy; lysosomes; mTOR; stress.

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Conflict of interest statement

DISCLOSURE STATEMENT

The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.

Figures

Figure 1.
Figure 1.. TFEB/TFE3 respond to different types of cellular stress.
Under normal conditions mTORC1 phosphorylates TFEB/TFE3, thus promoting their cytosolic retention. Following starvation (1), mTORC1 inactivation together with activation of specific phosphatases such as calcineurin, lead to TFEB/TFE3 nuclear translocation. TFEB/TFE3 activation is also observed in response to ER stress (2), mitochondrial damage (3), and pathogen infection (4). The proteins implicated in TFEB/TFE3 activation under different stress conditions are represented in blue.
Figure 2.
Figure 2.. TFEB/TFE3 regulate a complex transcriptional network critical for cellular adaptation to a variety of perturbations.
The primary role of TFEB/TFE3 may vary depending on cell type and includes metabolic regulation (hepatocytes), inflammatory response (macrophages), mitochondrial function (muscle), cellular clearance (neurons), and cell growth and survival (cancer cells).
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