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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., Pierre-Louis, T., Lenoir, O. and Huber, T. B. (2019) Podocytes maintain high basal levels of autophagy independent of mTOR signaling. Autophagy. ISSN 1554-8627 (In Press)

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Abstract/Summary

Autophagy and mTOR mediated regulation of cytoplasmic homeostasis and podocyte size are two key cellular mechanisms that underpin the integrity of the renal filtration barrier. Investigations of various tissues and cell lines support the notion that mTOR suppresses autophagy. In a translational context it has been proposed that induction of autophagy through the inhibition of mTOR activity could be of clinical benefit. Unexpectedly, we report that genetic manipulation of mTOR activity does not influence the high levels of basal autophagy in podocytes either in vitro or in vivo. Instead we present data showing that autophagy in podocytes is primarily controlled by AMP-activated protein kinase (AMPK) and Unc-51-like kinase 1 (ULK1). Pharmacologic inhibition of mTOR further reveals that the uncoupling of mTOR activity and autophagy is time-dependent. Thus, our data reveal a novel cell-specific mechanism, which permits concurrent mTOR activity as well as high basal autophagy rates in podocytes. Therefore, we advocate manipulating the AMPK-ULK1 axis rather than inhibiting mTOR as intervention strategy to enhance autophagy for the treatment of podocyte diseases.

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

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