What else is in store for autophagy? Exocytosis of autolysosomes as a mechanism of TFEB-mediated cellular clearance in Pompe disease

 Abstract

It is hard to find an area of biology in which autophagy is not involved. In fact, the topic extends beyond scientific research to stimulate intellectual exercise and entertainment—autophagy has found its way into a crossword puzzle (Klionsky, 2013). We have found yet another function of autophagy while searching for a better treatment for Pompe disease, a devastating metabolic myopathy resulting from excessive lysosomal glycogen storage. To relieve this glycogen burden, we stimulated lysosomal exocytosis through upregulation of transcription factor EB (TFEB). Overexpression of TFEB in Pompe muscle clears the cells of enlarged lysosomes, reduces glycogen levels, and alleviates autophagic buildup, the major secondary abnormality in Pompe disease. Unexpectedly, the process of exocytosis does not seem to be a purely lysosomal event; vesicles arranged along the plasma membrane are double-labeled with the lysosomal marker LAMP1 and the autophagosomal marker LC3, indicating that TFEB induces the exocytosis of autolysosomes. Furthermore, the effects of TFEB are almost abrogated in autophagy-deficient Pompe mice, suggesting a previously unrecognized role of autophagy in TFEB-mediated cellular clearance.

 Related Article:

C Spampanato, E Feeney, L Li, M Cardone, JA Lim, F Annunziata, et al. Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol Med 2013; 5: 691- 706.
PMID: 23606558 DOI: 10.1002/emmm.201202176

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Pages
1117 - 1118
doi
10.4161/auto.24920
Type
Autophagic Punctum
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What else is in store for autophagy? Exocytosis of autolysosomes as a mechanism of TFEB-mediated cellular clearance in Pompe disease