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Álvaro F. Fernández, Carlos López-Otín
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):33-41. https://doi.org/10.1172/JCI73940.
Citation Information: J Clin Invest. 2015;125(1):33-41. https://doi.org/10.1172/JCI73940.
Abstract
Autophagy is a well-conserved catabolic process essential for cellular homeostasis. First described in yeast as an adaptive response to starvation, this pathway is also present in higher eukaryotes, where it is triggered by stress signals such as damaged organelles or pathogen infection. Autophagy is characterized at the cellular level by the engulfment of portions of the cytoplasm in double-membrane structures called autophagosomes. Autophagosomes fuse with lysosomes, resulting in degradation of the inner autophagosomal membrane and luminal content. This process is coordinated by complex molecular systems, including the ATG8 ubiquitin–like conjugation system and the ATG4 cysteine proteases, which are implicated in the formation, elongation, and fusion of these autophagic vesicles. In this Review, we focus on the diverse functional roles of the autophagins, a protease family formed by the four mammalian orthologs of yeast Atg4. We also address the dysfunctional expression of these proteases in several pathologic conditions such as cancer and inflammation and discuss potential therapies based on their modulation.
Authors
Álvaro F. Fernández, Carlos López-Otín
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Citation information
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Scientific Reports | 2021 |
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Rab9 Mediates Pancreatic Autophagy Switch From Canonical to Noncanonical, Aggravating Experimental Pancreatitis
O Mareninova, D Dillon, C Wightman, I Yakubov, T Takahashi, H Gaisano, K Munson, M Ohmuraya, D Dawson, I Gukovsky, A Gukovskaya |
CMGH Cellular and Molecular Gastroenterology and Hepatology | 2021 |
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Lysosomotropic Features and Autophagy Modulators among Medical Drugs: Evaluation of Their Role in Pathologies
TA Korolenko, TP Johnston, V Vetvicka |
Molecules (Basel, Switzerland) | 2020 |
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Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice
OA Mareninova, W Jia, SR Gretler, CL Holthaus, DD Thomas, M Pimienta, DL Dillon, AS Gukovskaya, I Gukovsky, GE Groblewski |
Autophagy | 2020 |
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Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer
Y Zeng, M Chen, S Ganesh, S Hu, H Chen, IR Nabi |
PloS one | 2020 |
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Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes
I Tamargo-Gómez, ÁF Fernández, G Mariño |
International journal of molecular sciences | 2020 |
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SSPH I, a Novel Anti-Cancer Saponin, Inhibits Autophagy and Induces Apoptosis via ROS Accumulation and ERK1/2 Signaling Pathway in Hepatocellular Carcinoma Cells J Zhou, X Huang, H Qiu, R Gan, H Zhou, H Zhu, X Zhang, G Lu, G Liang |
OncoTargets and therapy | 2020 |
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miR-433 Inhibits Neuronal Growth and Promotes Autophagy in Mouse Hippocampal HT-22 Cell Line
C Xu, Q Bai, C Wang, Q Meng, Y Gu, Q Wang, W Xu, Y Han, Y Qin, S Jia, J Zhang, J Xu, J Li, M Chen, F Wang |
Frontiers in pharmacology | 2020 |
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Altered Basal Autophagy Affects Extracellular Vesicle Release in Cells of Lagotto Romagnolo Dogs With a Variant ATG4D
P Syrjä, M Palviainen, T Jokinen, K Kyöstilä, H Lohi, P Roosje, L Anderegg, T Leeb, A Sukura, EL Eskelinen |
Veterinary pathology | 2020 |
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LncRNA Sox2OT-V7 promotes doxorubicin-induced autophagy and chemoresistance in osteosarcoma via tumor-suppressive miR-142/miR-22
K Zhu, Y Yuan, J Wen, D Chen, W Zhu, Z Ouyang, W Wang |
Aging | 2020 |
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Autophagy and its role in regeneration and remodeling within invertebrate
Q Song, H Liu, H Zhen, B Zhao |
Cell & Bioscience | 2020 |
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Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways
C Yan, J Zhao, Y Qin, F Zhao, L Ji, J Zhang |
Molecular medicine reports | 2020 |
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LC3-associated phagocytosis at a glance
BL Heckmann, DR Green |
Journal of cell science | 2019 |
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Sevoflurane induces cognitive impairment in young mice via autophagy
X Wang, Y Dong, Y Zhang, T Li, Z Xie, H Wei |
PloS one | 2019 |
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Comprehensive autophagy evaluation in cardiac disease models
N Kaludercic, MC Maiuri, S Kaushik, ÁF Fernández, J de Bruijn, F Castoldi, Y Chen, J Ito, R Mukai, T Murakawa, J Nah, F Pietrocola, T Saito, S Sebti, M Semenzato, L Tsansizi, S Sciarretta, J Madrigal-Matute |
Cardiovascular Research | 2019 |
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On ATG4B as Drug Target for Treatment of Solid Tumours—The Knowns and the Unknowns
Agrotis, Ketteler |
Cells | 2019 |
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Mechanism of Stx17 recruitment to autophagosomes via IRGM and mammalian Atg8 proteins
S Kumar, A Jain, F Farzam, J Jia, Y Gu, SW Choi, MH Mudd, A Claude-Taupin, MJ Wester, KA Lidke, TE Rusten, V Deretic |
The Journal of Cell Biology | 2018 |
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ATG4B contains a C-terminal LIR motif important for binding and efficient cleavage of mammalian orthologs of yeast Atg8
MS Rasmussen, S Mouilleron, BK Shrestha, M Wirth, R Lee, KB Larsen, YA Princely, N O'Reilly, E Sjøttem, SA Tooze, T Lamark, T Johansen |
Autophagy | 2017 |
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A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes
J la Rosa, J Weber, MJ Friedrich, Y Li, L Rad, H Ponstingl, Q Liang, SB de Quirós, I Noorani, E Metzakopian, A Strong, MA Li, A Astudillo, MT Fernández-García, MS Fernández-García, GJ Hoffman, R Fuente, GS Vassiliou, R Rad, C López-Otín, A Bradley, J Cadiñanos |
Nature Genetics | 2017 |
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Autophagy and Its Impact on Neurodegenerative Diseases: New Roles for TDP-43 and C9orf72
M Budini, E Buratti, E Morselli, A Criollo |
Frontiers in molecular neuroscience | 2017 |
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Autophagy couteracts weight gain, lipotoxicity and pancreatic β-cell death upon hypercaloric pro-diabetic regimens
ÁF Fernández, C Bárcena, GG Martínez-García, I Tamargo-Gómez, MF Suárez, F Pietrocola, F Castoldi, L Esteban, E Sierra-Filardi, P Boya, C López-Otín, G Kroemer, G Mariño |
Cell Death and Disease | 2017 |
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Autophagy-regulating protease Atg4: structure, function, regulation and inhibition
T Maruyama, NN Noda |
The Journal of Antibiotics | 2017 |
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LC3-Associated Phagocytosis and Inflammation
BL Heckmann, E Boada-Romero, LD Cunha, J Magne, DR Green |
Journal of Molecular Biology | 2017 |
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ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy
M Antonelli, F Strappazzon, I Arisi, R Brandi, M D'Onofrio, M Sambucci, G Manic, I Vitale, D Barilà, V Stagni |
Oncotarget | 2017 |
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Nucleotide variation in ATG4A and susceptibility to cervical cancer in Southwestern Chinese women
JJ Mao, LX Wu, W Wang, YY Ye, J Yang, H Chen, QF Yang, XY Zhang, B Wang, WX Chen |
Oncology Letters | 2017 |
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mTORC1 activation decreases autophagy in aging and idiopathic pulmonary fibrosis and contributes to apoptosis resistance in IPF fibroblasts
Y Romero, M Bueno, R Ramirez, D Álvarez, JC Sembrat, EA Goncharova, M Rojas, M Selman, AL Mora, A Pardo |
Aging Cell | 2016 |
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Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes
Y Yang, L Chan |
Endocrine reviews | 2016 |
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Apoptosis, autophagy and unfolded protein response pathways in Arbovirus replication and pathogenesis
M Iranpour, AR Moghadam, M Yazdi, SR Ande, J Alizadeh, E Wiechec, R Lindsay, M Drebot, KM Coombs, S Ghavami |
Expert Reviews in Molecular Medicine | 2016 |
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Protease inhibition as new therapeutic strategy for GI diseases
N Vergnolle |
Gut | 2016 |
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Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions
MM Falk, CL Bell, RM Andrews, SA Murray |
BMC cell biology | 2016 |
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Role of chaperone-mediated autophagy in metabolism
I Tasset, AM Cuervo |
FEBS Journal | 2016 |
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Quo vadis? Interferon-inducible GTPases go to their target membranes via the LC3-conjugation system of autophagy
J Choi, SB Biering, S Hwang |
Small GTPases | 2016 |
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Autophagy Is Involved in the Sevoflurane Anesthesia-Induced Cognitive Dysfunction of Aged Rats
X Zhang, Y Zhou, M Xu, G Chen, D Blum |
PloS one | 2016 |
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ATG4A promotes tumor metastasis by inducing the epithelial-mesenchymal transition and stem-like properties in gastric cells
SW Yang, YF Ping, YX Jiang, X Luo, X Zhang, XW Bian, PW Yu |
Oncotarget | 2016 |
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Chloroquine Sensitizes Nasopharyngeal Carcinoma Cells but Not Nasoepithelial Cells to Irradiation by Blocking Autophagy
A Makowska, M Eble, K Prescher, M Hoß, U Kontny, I Ulasov |
PloS one | 2016 |
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Identification of breast cancer cell subtypes sensitive to ATG4B inhibition
S Bortnik, C Choutka, HM Horlings, S Leung, JH Baker, C Lebovitz, WH Dragowska, NE Go, MB Bally, AI Minchinton, KA Gelmon, SM Gorski |
Oncotarget | 2016 |
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Autophagy: a druggable process that is deregulated in aging and multiple human diseases
Guido Kroemer |
Journal of Clinical Investigation | 2015 |
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Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis
S Cabrera, M Maciel, I Herrera, T Nava, F Vergara, M Gaxiola, C López-Otín, M Selman, A Pardo |
Autophagy | 2015 |
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Redox regulation of autophagy in healthy brain and neurodegeneration
K Hensley, ME Harris-White |
Neurobiology of Disease | 2015 |
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The Degradome database: expanding roles of mammalian proteases in life and disease
JG Pérez-Silva, Y Español, G Velasco, V Quesada |
Nucleic Acids Research | 2015 |
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Biochemical Characterization and Substrate Specificity of Autophagin-2 from the Parasite Trypanosoma cruzi
J Rajković, M Poreba, D Caglič, R Vidmar, A Wilk, A Borowik, G Salvesen, V Turk, M Drag, B Turk |
The Journal of biological chemistry | 2015 |
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