A Gene Network Regulating Lysosomal Biogenesis and Function

@article{Sardiello2009AGN,
  title={A Gene Network Regulating Lysosomal Biogenesis and Function},
  author={Marco Sardiello and Michela Palmieri and Alberto di Ronza and Diego Luis Medina and Marta Valenza and Vincenzo Alessandro Gennarino and Chiara Di Malta and Francesca Donaudy and Valerio Embrione and Roman S. Polishchuk and Sandro Banfi and Giancarlo Parenti and Elena Cattaneo and Andrea Ballabio},
  journal={Science},
  year={2009},
  volume={325},
  pages={473 - 477}
}
Master Controller Cellular organelles allow the localized regulation of specialized processes. Under certain conditions, such as increased growth, organelles may be required to alter their function. Coordinated regulation of the gene networks required for mitochondrial and endoplasmic reticulum function has been observed. Now, Sardiello et al. (p. 473; published online 25 June) have discovered a gene network regulating the lysosome, the major organelle involved in the degradation of… 

Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways.

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The modulation of lysosome function could be a promising therapeutic strategy for the treatment of cancer as well as metabolic and neurodegenerative disorders.

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TFEB‐mediated enhancement of lysosomal biogenesis is highlighted and function as a candidate strategy to counteract the progression of these diseases.

Endocytic regulation of cellular ion homeostasis controls lysosome biogenesis

Exo-endocytosis of a Na + /H + exchanger controls lysosome biogenesis through Ca 2+ /calcineurin-mediated activation of TFEB in response to osmotic stress to promote the turnover of toxic proteins and cell survival.

Transcription factor EB: from master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases

  • M. Sardiello
  • Biology
    Annals of the New York Academy of Sciences
  • 2016
Interestingly, impaired TFEB signaling has been suggested to be a contributing factor in the pathogenesis of several degenerative storage diseases and is highlighted as a candidate therapeutic target for the treatment of various degenerative diseases.

TFEB and the CLEAR network.

The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis

TFEB is identified as a target of mTOR and a mechanism for matching the transcriptional regulation of genes encoding proteins of autophagosomes and lysosomes to cellular need is suggested.

The Nutrient-Responsive Transcription Factor TFE3 Promotes Autophagy, Lysosomal Biogenesis, and Clearance of Cellular Debris

The identification of transcription factor E3 (TFE3) as another regulator of lysosomal homeostasis that induced expression of genes encoding proteins involved in autophagy and lYSosomal biogenesis in ARPE-19 cells in response to starvation and lysOSomal stress is reported.

TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator

New insights into novel post-translational modifications that regulate TFEB activity are provided and its widely known role in autophagy and the lysosomal pathway is given, thus opening the possibility of considering T FEB as a potential therapeutic target.

The cellular pathology of lysosomal diseases

The cryptic evolution of events leading to irreversible changes may be dissociated from the cellular storage phenotype, as revealed by the outcome of therapeutic gene transfer undertaken at different stages of disease.
...

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