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AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

Dohmen, Marc, Krieg, Sarah, Agalaridis, Georgios, Zhu, Xiaoqing, Shehata, Saifeldin N., Pfeiffenberger, Elisabeth, Amelang, Jan, Bütepage, Mareike, Buerova, Elena, Pfaff, Carolina M., Chanda, Dipanjan, Geley, Stephan, Preisinger, Christian, Sakamoto, Kei, Lüscher, Bernhard, Neumann, Dietbert, Vervoorts, Jörg·2020·Nature Communications
DOI 10.1038/s41467-020-14812-0PMC PMC7042329
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Abstract

The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. Using protein microarrays, we identify Cyclin Y as an AMPK substrate that is phosphorylated at Serine 326 (S326) both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the Cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.

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Metadata

Authors
Dohmen, M., Krieg, S., Agalaridis, G., Zhu, X., Shehata, S. N., Pfeiffenberger, E., Amelang, J., Bütepage, M., Buerova, E., Pfaff, C. M., Chanda, D., Geley, S., Preisinger, C., Sakamoto, K., Lüscher, B., Neumann, D., & Vervoorts, J.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-02-25
Volume
11
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-020-14812-0
PMC
PMC7042329
Cited by
40
References
5
Language
en
Licence
Funders
  • Chinese Scholarship Council
  • Marie Curie fellowship
  • Deutsche Forschungsgemeinschaft (LU 466/16-2)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.10.007)

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