Regulation of Autophagy Enzymes by Nutrient Signaling.

Karyn E King, Truc T Losier, Ryan C Russell

Journal: Trends in biochemical sciences 2021;46(8):687-700

PMID: 33593593

Full Text on Elsevier Science View on PubMed

Abstract

Autophagy is the primary catabolic program of the cell that promotes survival in response to metabolic stress. It is tightly regulated by a suite of kinases responsive to nutrient status, including mammalian target of rapamycin complex 1 (mTORC1), AMP-activated protein kinase (AMPK), protein kinase C-α (PKCα), MAPK-activated protein kinases 2/3 (MAPKAPK2/3), Rho kinase 1 (ROCK1), c-Jun N-terminal kinase 1 (JNK), and Casein kinase 2 (CSNK2). Here, we highlight recently uncovered mechanisms linking amino acid, glucose, and oxygen levels to autophagy regulation through mTORC1 and AMPK. In addition, we describe new pathways governing the autophagic machinery, including the Unc-51-like (ULK1), vacuolar protein sorting 34 (VPS34), and autophagy related 16 like 1 (ATG16L1) enzyme complexes. Novel downstream targets of ULK1 protein kinase are also discussed, such as the ATG16L1 subunit of the microtubule-associated protein 1 light chain 3 (LC3)-lipidating enzyme and the ATG14 subunit of the VPS34 complex. Collectively, we describe the complexities of the autophagy pathway and its role in maintaining cellular nutrient homeostasis during times of starvation.

Address: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ONT, Canada.; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ONT, Canada; Center for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ONT, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ONT, Canada. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2021.01.006