Accessibility navigation


Podocytes maintain high basal levels of autophagy independent of mTOR signaling

Bork, T., Liang, W., Yamahara, K., Lee, P., Tian, Z., Liu, S., Schell, C., Thedieck, K., Hartleben, B., Patel, K., Tharaux, P.-L., Lenoir, O. and Huber, T. B. (2019) Podocytes maintain high basal levels of autophagy independent of mTOR signaling. Autophagy, 16 (11). pp. 1932-1948. ISSN 1554-8627

[img]
Preview
Text - Accepted Version
· Please see our End User Agreement before downloading.

528kB

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1080/15548627.2019.1705007

Abstract/Summary

While constant basal levels of macroautophagy/autophagy are a prerequisite to preserve long-lived podocytes at the filtration barrier, MTOR regulates at the same time podocyte size and compensatory hypertrophy. Since MTOR is known to generally suppress autophagy, the apparently independent regulation of these two key pathways of glomerular maintenance remained puzzling. We now report that long-term genetic manipulation of MTOR activity does in fact not influence high basal levels of autophagy in podocytes either in vitro or in vivo. Instead we present data showing that autophagy in podocytes is mainly controlled by AMP-activated protein kinase (AMPK) and ULK1 (unc-51 like kinase 1). Pharmacological inhibition of MTOR further shows that the uncoupling of MTOR activity and autophagy is time dependent. Together, our data reveal a novel and unexpected cell-specific mechanism, which permits concurrent MTOR activity as well as high basal autophagy rates in podocytes. Thus, these data indicate manipulation of the AMPK-ULK1 axis rather than inhibition of MTOR as a promising therapeutic intervention to enhance autophagy and preserve podocyte homeostasis in glomerular diseases.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:83847
Publisher:Taylor & Francis

Downloads

Downloads per month over past year

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation