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. (2020) Podocytes maintain high basal levels of autophagy independent of mTOR signaling. Autophagy, 16 (11). pp. 1932-1948. ISSN 1554-8627 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
URI	https://reading-clone.eprints-hosting.org/id/eprint/83847
Identification Number/DOI	10.1080/15548627.2019.1705007
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Taylor & Francis
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