Format

Send to

Choose Destination
Autophagy. 2013 Jul;9(7):1117-8. doi: 10.4161/auto.24920. Epub 2013 May 6.

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

Author information

1
Laboratory of Muscle Stem Cells and Gene Regulation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health; Bethesda, MD USA.

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.

KEYWORDS:

Pompe disease; TFEB; acid alpha-glucosidase; lysosomal exocytosis; lysosomal storage

PMID:
23669057
PMCID:
PMC3722326
DOI:
10.4161/auto.24920
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center