bims-nocaut 2023-07-16 papers

Issue of 2023–07–16
three papers selected by
Quentin Frenger, University of Strasbourg

Autophagy. 2023 Jul 09. 1-3

The autophagy-related protein ATG5 is a central mediator of a non-canonical autophagy pathway hijacked by HIV-1 to weaken the host's response to infection.

Delphine Judith, Clarisse Berlioz-Torrent.

Understanding how viruses evade innate defenses to efficiently spread in their hosts is crucial in the fight against infections. In our study, we provided new insights on the first step initiating an LC3C (microtubule associated protein 1 light chain 3 gamma)-associated degradative pathway exploited by HIV-1 (human immunodeficiency virus type 1) to overcome the antiviral action of the restriction factor BST2 (bone marrow stromal cell antigen 2)/tetherin. We have uncovered an unsuspected and unconventional function of the autophagy-related protein ATG5 in the recognition and engagement of BST2 molecules trapping viruses at the plasma membrane, and directing them toward this LC3C-associated pathway for degradation. Additionally, we highlighted that HIV-1 uses this LC3C-associated process to attenuate the inflammatory responses triggered by BST2-mediated sensing of viruses.

Keywords: ATG5; BST2; HIV-1; LC3C-associated pathway; Vpu; restriction factor

DOI: https://doi.org/10.1080/15548627.2023.2232225

Autophagy Rep. 2022 ;1(1): 438-515

Interactions of Autophagy and the Immune System in Health and Diseases.

Aarti Pant, Xiaomin Yao, Aude Lavedrine, Christophe Viret, Jake Dockterman, Swati Chauhan, Chong-Shan Shi, Ravi Manjithaya, Ken Cadwell, Thomas A Kufer, John H Kehrl, Jörn Coers, L David Sibley, Mathias Faure, Gregory A Taylor, Santosh Chauhan.

Autophagy is a highly conserved process that utilizes lysosomes to selectively degrade a variety of intracellular cargo, thus providing quality control over cellular components and maintaining cellular regulatory functions. Autophagy is triggered by multiple stimuli ranging from nutrient starvation to microbial infection. Autophagy extensively shapes and modulates the inflammatory response, the concerted action of immune cells, and secreted mediators aimed to eradicate a microbial infection or to heal sterile tissue damage. Here, we first review how autophagy affects innate immune signaling, cell-autonomous immune defense, and adaptive immunity. Then, we discuss the role of non-canonical autophagy in microbial infections and inflammation. Finally, we review how crosstalk between autophagy and inflammation influences infectious, metabolic, and autoimmune disorders.

DOI: https://doi.org/10.1080/27694127.2022.2119743

Mol Cell Biochem. 2023 Jul 13.

A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.

Jiawei Chen, Hong Zhao, Meiqing Liu, Linxi Chen.

Mammalian autophagy-related protein Atg8, including the LC3 subfamily and GABARAP subfamily. Atg8 proteins play a vital role in autophagy initiation, autophagosome formation and transport, and autophagy-lysosome fusion. GABARAP subfamily proteins (GABARAPs) share a high degree of homology with LC3 family proteins, and their unique roles are often overlooked. GABARAPs are as indispensable as LC3 in autophagy. Deletion of GABARAPs fails autophagy flux induction and autophagy lysosomal fusion, which leads to the failure of autophagy. GABARAPs are also involved in the transport of selective autophagy receptors. They are engaged in various particular autophagy processes, including mitochondrial autophagy, endoplasmic reticulum autophagy, Golgi autophagy, centrosome autophagy, and dorphagy. Furthermore, GABARAPs are closely related to the transport and delivery of the inhibitory neurotransmitter γ-GABAA and the angiotensin II AT1 receptor (AT1R), tumor growth, metastasis, and prognosis. GABARAPs also have been confirmed to be involved in various diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In order to better understand the role and therapeutic potential of GABARAPs, this article comprehensively reviews the autophagic and non-autophagic functions of GABARAPs, as well as the research progress of the role and mechanism of GABARAPs in cancer, cardiovascular diseases and neurodegenerative diseases. It emphasizes the significance of GABARAPs in the clinical prevention and treatment of diseases, and may provide new therapeutic ideas and targets for human diseases. GABARAP and GABARAPL1 in the serum of cancer patients are positively correlated with the prognosis of patients, which can be used as a clinical biomarker, predictor and potential therapeutic target. GABARAP family proteins: autophagy and non-autophagy related functions in diseases. By Figdraw ( https://www.figdraw.com ).

Keywords: Cancer; Cardiovascular diseases; GABARAP/LC3; Immune inflammatory response; Neurodegenerative disease; Selective autophagy

DOI: https://doi.org/10.1007/s11010-023-04800-5