Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks
Open accessAbstract
Living cells are adaptive self-sustaining systems. They strictly depend on the sufficient supply of oxygen, energy, and nutrients from the outside in order to sustain their internal organization. However, as autonomous entities they are able to monitor and appropriately adapt to any critical fluctuation in their environment. In the case of insufficient external nutrient supply or augmented energy demands, cells start to extensively digest their own interior. This process, known as macroautophagy, comprises the transport of cytosolic portions and entire organelles to the lysosomal compartment via specific double-membrane vesicles, called autophagosomes. Although extensively upregulated under nutrient restriction, a low level of basal autophagy is likewise crucial in order to sustain the cellular homeostasis. On the other hand, cells have to avoid excessive and enduring self-digestion. The delicate balance between external energy and nutrient supply and internal production and consumption is a demanding task. The complex protein network that senses and precisely reacts to environmental changes is thus mainly regulated by rapid and reversible posttranslational modifications such as phosphorylation. This review focuses on the serine/threonine protein kinases AMP-activated protein kinase, mammalian target of rapamycin (mTOR), and unc-51-like kinase 1/2 (Ulk1/2), three interconnected major junctions within the autophagy regulating signaling network.
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AMPK positively regulates autophagy by phosphorylating ULK-1 and ULK-2 in their activating sites.
“AMPK positively regulates autophagy by phosphorylating these proteins in their activating sites”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Alers et al., 2012
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Flagged first, then by citations
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- Authors
- Alers, S., Löffler, A. S., Wesselborg, S., & Stork, B.
- Affiliations
- Universitätsklinikum Tübingen (DE)
- Corresponding author
- Alers, Sebastian
- Stork, Björn
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2012-01-01
- Volume
- 32
- Issue
- 1
- Pages
- 2-11
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3255710
- OpenAlex
- W2102776209
- Cited by
- 1,483
- References
- 123
- Citations by year
- 2026: 54 · 2025: 119 · 2024: 151 · 2023: 117 · 2022: 140 · 2021: 121 · 2020: 126 · 2019: 96 · 2018: 97 · 2017: 101 · 2016: 98 · 2015: 93 · 2014: 74 · 2013: 57 · 2012: 37
- FWCI
- 40.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- autophagy regulation, AMPK, mTOR, macroautophagy, autophagosome formation, nutrient sensing, energy homeostasis, post-translational modification, phosphorylation, signaling networks, lysosomal degradation, cellular homeostasis
- MeSH terms
- Animals, Autophagy, Humans, Signal Transduction, Protein Serine-Threonine Kinases, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
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