PAQR 3 controls autophagy by integrating AMPK signaling to enhance ATG 14L‐associated PI 3K activity
Abstract: The Beclin1–VPS34 complex is recognized as a central node in regulating autophagy via interacting with diverse molecules such as ATG14L for autophagy initiation and UVRAG for autophagosome maturation. However, the underlying molecular mechanism that coordinates the timely activation of VPS34 complex is poorly understood. Here, we identify that PAQR3 governs the preferential formation and activation of ATG14L‐linked VPS34 complex for autophagy initiation via two levels of regulation. Firstly, PAQR3 functions as a scaffold protein that facilitates the formation of ATG14L‐ but not UVRAG‐linked VPS34 complex, leading to elevated capacity of PI (3) P generation ahead of starvation signals. Secondly, AMPK phosphorylates PAQR3 at threonine 32 and switches on PI (3) P production to initiate autophagosome formation swiftly after glucose starvation. Deletion of PAQR3 leads to reduction of exercise‐induced autophagy in mice, accompanied by a certain degree of disaggregation of ATG14L‐associated VPS34 complex. Together, this study uncovers that PAQR3 can not only enhance the capacity of pro‐autophagy class III PI3K due to its scaffold function, but also integrate AMPK signal to activation of ATG14L‐linked VPS34 complex upon glucose starvation.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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PAQR 3 controls autophagy by integrating AMPK signaling to enhance ATG 14L‐associated PI 3K activity ; volume:35 ; number:5 ; year:2016 ; pages:496-514 ; extent:19
The EMBO journal / European Molecular Biology Organization ; 35, Heft 5 (2016), 496-514 (gesamt 19)
- Urheber
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Xu, Da‐Qian
Wang, Zheng
Wang, Chen‐Yao
Zhang, De‐Yi
Wan, Hui‐Da
Zhao, Zi‐Long
Gu, Jin
Zhang, Yong‐Xian
Li, Zhi‐Gang
Man, Kai‐Yang
Pan, Yi
Wang, Zhi‐Fei
Ke, Zun‐Ji
Liu, Zhi‐Xue
Liao, Lu‐Jian
Chen, Yan
- DOI
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10.15252/embj.201592864
- URN
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urn:nbn:de:101:1-2022111504540445083374
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:36 MESZ
Datenpartner
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Beteiligte
- Xu, Da‐Qian
- Wang, Zheng
- Wang, Chen‐Yao
- Zhang, De‐Yi
- Wan, Hui‐Da
- Zhao, Zi‐Long
- Gu, Jin
- Zhang, Yong‐Xian
- Li, Zhi‐Gang
- Man, Kai‐Yang
- Pan, Yi
- Wang, Zhi‐Fei
- Ke, Zun‐Ji
- Liu, Zhi‐Xue
- Liao, Lu‐Jian
- Chen, Yan
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