In situ structural analysis reveals membrane shape transitions during autophagosome formation DOI Creative Commons
Anna Bieber, Cristina Capitanio, Philipp S. Erdmann

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(39)

Опубликована: Сен. 19, 2022

Autophagosomes are unique organelles that form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves membrane transformations of distinctly shaped intermediates whose ultrastructure is poorly understood. Here, we combine cell biology, correlative cryo-electron tomography (cryo-ET), and extensive data analysis to reveal the step-by-step structural progression autophagosome at high resolution directly within yeast cells. The uncovers an unexpectedly thin intermembrane distance dilated phagophore rim. Mapping individual autophagic structures onto a timeline based on geometric features reveals dynamical change shape curvature in growing phagophores. Moreover, our tomograms show organelle interactome autophagosomes, highlighting polar organization contact sites between organelles, such vacuole endoplasmic reticulum (ER). Collectively, these findings have important implications contribution different sources during autophagy forces shaping driving phagophores toward closure without templating cargo.

Язык: Английский

Autophagy in major human diseases DOI Creative Commons
Daniel J. Klionsky, Giulia Petroni, Ravi K. Amaravadi

и другие.

The EMBO Journal, Год журнала: 2021, Номер 40(19)

Опубликована: Авг. 30, 2021

Review30 August 2021Open Access Autophagy in major human diseases Daniel J Klionsky orcid.org/0000-0002-7828-8118 Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA Search for more papers by this author Giulia Petroni Department Radiation Oncology, Weill Cornell Medical College, New York, NY, Ravi K Amaravadi Medicine, Pennsylvania, Philadelphia, PA, Abramson Cancer Center, Eric H Baehrecke Molecular, Cell and Biology, Massachusetts School, Worcester, MA, Andrea Ballabio orcid.org/0000-0003-1381-4604 Telethon Institute Genetics Pozzuoli, Italy Translational Sciences, Section Pediatrics, Federico II University, Naples, Molecular Human Genetics, Baylor College Jan Dan Duncan Neurological Research Texas Children Hospital, Houston, TX, Patricia Boya orcid.org/0000-0003-3045-951X Margarita Salas Center Biological Research, Spanish National Council, Madrid, Spain José Manuel Bravo-San Pedro Faculty Physiology, Complutense Networked Biomedical Neurodegenerative Diseases (CIBERNED), Ken Cadwell Kimmel Biology Medicine at the Skirball York Grossman School Microbiology, Division Gastroenterology Hepatology, Langone Health, Francesco Cecconi orcid.org/0000-0002-5614-4359 Stress Survival Unit, Autophagy, Recycling Disease (CARD), Danish Society Copenhagen, Denmark Pediatric Onco-Hematology Gene Therapy, IRCCS Bambino Gesù Children's Rome, Rome 'Tor Vergata', Augustine M Choi Pulmonary Critical Care Joan Sanford I. York-Presbyterian Mary E Nephrology Hypertension, Charleen T Chu orcid.org/0000-0002-5052-8271 Pathology, Pittsburgh Pittsburgh, Patrice Codogno orcid.org/0000-0002-5492-3180 Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Paris, France Université de Maria Isabel Colombo Laboratorio Mecanismos Moleculares Implicados en el Tráfico Vesicular y la Autofagia-Instituto Histología Embriología (IHEM)-Universidad Nacional Cuyo, CONICET- Facultad Ciencias Médicas, Mendoza, Argentina Ana Cuervo orcid.org/0000-0002-0771-700X Developmental Albert Einstein Bronx, Aging Studies, Vojo Deretic Inflammation Metabolism (AIM, Excellence, Mexico Health Albuquerque, NM, Ivan Dikic orcid.org/0000-0001-8156-9511 Biochemistry II, Goethe Frankfurt, Frankfurt am Main, Germany Buchmann Zvulun Elazar Biomolecular The Weizmann Science, Rehovot, Israel Eeva-Liisa Eskelinen Biomedicine, Turku, Finland Gian Fimia orcid.org/0000-0003-4438-3325 Sapienza Epidemiology, Preclinical Advanced Diagnostics, Infectious 'L. Spallanzani' IRCCS, David A Gewirtz orcid.org/0000-0003-0437-4934 Pharmacology Toxicology, Virginia Commonwealth Richmond, VA, Douglas R Green Immunology, St. Jude Memphis, TN, Malene Hansen Burnham Prebys Discovery Program Development, Aging, Regeneration, La Jolla, CA, Marja Jäättelä orcid.org/0000-0001-5950-7111 Death Metabolism, & Disease, Cellular Terje Johansen orcid.org/0000-0003-1451-9578 Group, Tromsø—The Arctic Norway, Tromsø, Norway Gábor Juhász Szeged, Hungary Anatomy, Eötvös Loránd Budapest, Vassiliki Karantza Merck Co., Inc., Kenilworth, NJ, Claudine Kraft orcid.org/0000-0002-3324-4701 ZBMZ, Freiburg, CIBSS - Centre Integrative Signalling Guido Kroemer orcid.org/0000-0002-9334-4405 Recherche des Cordeliers, Equipe Labellisée par Ligue Contre le Cancer, Sorbonne Université, Inserm U1138, Universitaire France, Metabolomics Platforms, Gustave Roussy, Villejuif, Pôle Biologie, Hôpital Européen Georges Pompidou, AP-HP, Suzhou Systems Chinese Academy Suzhou, China Karolinska Women's Stockholm, Sweden Nicholas Ktistakis Programme, Babraham Cambridge, UK Sharad Kumar orcid.org/0000-0001-7126-9814 South Australia, Adelaide, SA, Australia Carlos Lopez-Otin orcid.org/0000-0001-6964-1904 Departamento Bioquímica Biología Medicina, Instituto Universitario Oncología del Principado Asturias (IUOPA), Universidad Oviedo, Centro Investigación Biomédica Red Cáncer (CIBERONC), Kay F Macleod Ben May Gordon W-338, Chicago, IL, Frank Madeo Biosciences, NAWI Graz, Austria BioTechMed-Graz, Field Excellence BioHealth – Jennifer Martinez Immunity, Laboratory, Environmental NIH, Triangle Park, NC, Alicia Meléndez Department, Queens City Flushing, Graduate PhD Programs Noboru Mizushima orcid.org/0000-0002-6258-6444 Tokyo, Japan Christian Münz orcid.org/0000-0001-6419-1940 Viral Immunobiology, Experimental Zurich, Switzerland Josef Penninger Biotechnology Austrian (IMBA), Vienna BioCenter (VBC), Vienna, British Columbia, Vancouver, BC, Canada Rushika Perera orcid.org/0000-0003-2435-2273 California, San Francisco, Helen Diller Family Comprehensive Mauro Piacentini orcid.org/0000-0003-2919-1296 "Tor Vergata", Laboratory Cytology Russian Saint Petersburg, Russia Fulvio Reggiori orcid.org/0000-0003-2652-2686 Cells Systems, Section, Groningen, Netherlands C Rubinsztein Cambridge Dementia Kevin Ryan Beatson Glasgow, Junichi Sadoshima Cardiovascular Rutgers Jersey Newark, Laura Santambrogio Sandra Edward Meyer Caryl Englander Precision Luca Scorrano orcid.org/0000-0002-8515-8928 Istituto Veneto di Medicina Molecolare, Padova, Hans-Uwe Simon Pharmacology, Bern, Clinical Immunology Allergology, Sechenov Moscow, Fundamental Kazan Federal Kazan, Anna Katharina Kennedy Rheumatology, NDORMS, Oxford, Anne Simonsen orcid.org/0000-0003-4711-7057 Basic Oslo, Reprogramming, Oslo Hospital Montebello, Alexandra Stolz orcid.org/0000-0002-3340-439X Nektarios Tavernarakis orcid.org/0000-0002-5253-1466 Biotechnology, Foundation Technology-Hellas, Heraklion, Crete, Greece Sharon Tooze orcid.org/0000-0002-2182-3116 Francis Crick London, Tamotsu Yoshimori orcid.org/0000-0001-9787-3788 Osaka Suita, Intracellular Membrane Dynamics, Frontier Integrated Science Division, Open Transdisciplinary Initiatives (OTRI), Junying Yuan Interdisciplinary on Chemistry, Shanghai Organic Shanghai, Harvard Boston, Zhenyu Yue Neurology, Friedman Brain Icahn Mount Sinai, Qing Zhong orcid.org/0000-0001-6979-955X Key Differentiation Apoptosis Ministry Education, Pathophysiology, Jiao Tong (SJTU-SM), Lorenzo Galluzzi Corresponding Author [email protected] orcid.org/0000-0003-2257-8500 Dermatology, Yale Haven, CT, Pietrocola orcid.org/0000-0002-2930-234X Biosciences Nutrition, Huddinge, mor

Язык: Английский

Процитировано

1117

Molecular mechanisms and physiological functions of mitophagy DOI Creative Commons
Mashun Onishi, Koji Yamano, Miyuki Sato

и другие.

The EMBO Journal, Год журнала: 2021, Номер 40(3)

Опубликована: Янв. 13, 2021

Review13 January 2021Open Access Molecular mechanisms and physiological functions of mitophagy Mashun Onishi orcid.org/0000-0003-1511-4097 Laboratory Mitochondrial Dynamics, Graduate School Frontier Biosciences, Osaka University, Suita, JapanThese authors contributed equally to this work Search for more papers by author Koji Yamano orcid.org/0000-0002-4692-161X The Ubiquitin Project, Tokyo Metropolitan Institute Medical Science, Tokyo, Miyuki Sato Corresponding Author [email protected] orcid.org/0000-0002-1944-4918 Membrane Biology, Cellular Regulation, Gunma Maebashi, Japan Noriyuki Matsuda orcid.org/0000-0001-8199-952X Okamoto orcid.org/0000-0003-4730-4522 Information Onishi1, Yamano2, *,3, *,2 *,1 1Laboratory 2The 3Laboratory *Corresponding author. Tel: +81 27 220 8842; E-mail: 3 5316 3244; 6 6879 7970; EMBO Journal (2021)40:e104705https://doi.org/10.15252/embj.2020104705 See the Glossary abbreviations used in article. PDFDownload PDF article text main figures. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Degradation mitochondria via a selective form autophagy, named mitophagy, is fundamental mechanism conserved from yeast humans that regulates mitochondrial quality quantity control. Mitophagy promoted specific outer membrane receptors, or ubiquitin molecules conjugated proteins on surface leading formation autophagosomes surrounding mitochondria. Mitophagy-mediated elimination plays an important role many processes including early embryonic development, cell differentiation, inflammation, apoptosis. Recent advances analyzing vivo also reveal high rates steady-state turnover diverse types, highlighting intracellular housekeeping mitophagy. Defects are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, aging, further underscoring biological relevance. Here, we review our current molecular understanding its implications, discuss how multiple pathways coordinately modulate fitness populations. ALLO-1 Allophagy-1 ATG Autophagy-related protein BCL2L1/BCL-XL BCL2 like 1 BCL2L13 B-cell lymphoma 2-like 13 BNIP3 adenovirus E1B 19-kDa-interacting BNIP3L Nip3-like X (NIX)/BNIP3-like CCCP Carbonyl cyanide m-chlorophenylhydrazone cGAS Cyclic GMP-AMP synthase CK2 Casein kinase 2 CPS-6 endonuclease G DFCP1/ZFYVE1 DFCP1/zinc finger FYVE-type containing FIP200/RB1CC1 FIP200/RB1-inducible coiled-coil Fis1 Fission, FKBP8/FKBP38 FK506-binding 8 FOXO1 Forkhead box O1 FUNDC1 FUN14 domain-containing GABARAP GABA type A receptor-associated GABARAPL1/2 protein-like 1/2 GFP Green fluorescent HOPS Homotypic fusion vacuole sorting IGF-1 Insulin-like growth factor Keap1 Kelch-like ECH-associated LC3A/B/C Microtubule-associated light chain alpha/beta/gamma LIR LC3-interacting region MARCH5/MITOL Membrane-associated ring-CH-type 5 MBP Maltose-binding Miro Rho mTORC1 Mechanistic target rapamycin complex MUL1 E3 ligase NBR1 autophagy cargo receptor NDP52/CALCOCO2 NDP52/calcium binding domain NLRP3 NLR family pyrin NOD Nucleotide-binding oligomerization NRF2 Nuclear factor, erythroid OPTN Optineurin p62/SQSTM1 p62/Sequestosome PARL Presenilin-associated rhomboid-like PC Phosphatidylcholine PE Phosphatidylethanolamine PGAM5 PGAM member 5, serine/threonine phosphatase PI Phosphatidylinositol PI3K 3-kinase PI3P Phosphatidylinositol-3-phosphate PINK1 PTEN induced PLEKHM1 Pleckstrin homology RUN M1 RABGEF1 RAB guanine nucleotide exchange Rheb Ras homolog, SNARE Soluble N-ethylmaleimide-sensitive attachment Src SRC proto-oncogene, non-receptor tyrosine STING Stimulator interferon genes TAX1BP1 Tax1 TBC1D15 TBC1 15 TBC1D17 17 TBK1 TANK-binding TOMM/TOM Translocase TORC1 Target UBAN Ubiquitin-binding ABIN NEMO ULK1 Unc-51-like activating USP protease VDAC Voltage-dependent anion channel VPS Vacuolar WIPI WD repeat domain, phosphoinositide interacting Introduction Mitochondria double-membrane-bound subcellular compartments function ATP production, phospholipid biosynthesis/transport, calcium signaling, iron homeostasis (Raffaello et al, 2016; Tamura Endo, 2017; Spinelli Haigis, 2018). These organelles act platforms events apoptosis, innate immune response, differentiation (Mehta Kalkavan Green, 2018; Lisowski Since generate reactive oxygen species (ROS) electron transport chain, they constantly challenged oxidative stress ultimately may lead their structural functional failure (Wong 2017). Therefore, cells need sophisticated systems maintaining fitness. control relies pathways: ROS scavenging, DNA repair, refolding/degradation (Scheibye-Knudsen 2015). In addition these processes, fission play key roles (Eisner While promotes content mixing between healthy partially dysfunctional mitochondria, separates damaged components pool. autophagic system targets impaired delivers them lysosomes degradation. This catabolic process, called contributes (Pickles 2018) types. tissues consuming large amount brain, skeletal muscle, heart, liver, kidney, highly developed order maintain proper balance energy demand supply. When shifted normoxia hypoxia, decrease quantity, thereby adapting cellular metabolism anaerobic (Wu Chen, Thus, biogenesis degradation two opposing determine (Ploumi addition, almost completely eliminated during erythrocyte maturation (Ney, Furthermore, accumulating evidence reveals maternal inheritance (mtDNA) depends clearance sperm-derived paternal embryogenesis (Sato Sato, Although generally recognized bulk process non-selectively transports cytoplasmic nucleic acids, proteins, (Nakatogawa, 2020), it acts mediate particular (Gatica one organelle-specific serves structure (Okamoto, 2014) (Fig 1). term "mitophagy" was first coined 2005 (Lemasters, 2005; Priault 2005), within few years, major breakthroughs led discovery selectively (Okamoto 2009; Kanki 2009b) mammalian (Schweers 2007; Narendra 2008; Sandoval 2008). review, will describe underlying yeast, worms, Drosophila, cover pathophysiological functions. Figure 1. Overview (1) Intra- extracellular cues promote isolation excess fragmentation tubular networks. (2) receptors ubiquitin–autophagy adaptors confer selectivity recruited and/or activated (3) Core autophagy-related membrane/phagophore (4) Targeted enclosed sequestrated autophagosomes. (5) Autophagosomes transported fused lytic vacuoles mammals. (6) Lysosomal vacuolar acidic hydrolases flow into degrade contents be recycled. Download figure PowerPoint Receptor-mediated Regulation Atg32 budding Saccharomyces cerevisiae mostly mediated Atg32, single-pass transmembrane (OMM) 2009) 2A). unicellular eukaryote, when grown stationary phase upon nitrogen starvation (Tal Klionsky, 2009). Under conditions, expression at transcriptional level accumulates OMM, forming Atg8 Atg11 localized autophagosomes, scaffold other Atg autophagosome formation. Loss abolishes while overexpression increases activity, suggesting molecule rate-limiting regulating number degraded. specifically dispensable types cytoplasm-to-vacuole targeting pathway, ER-phagy, pexophagy. 2. (A) Schematic representation structures AIM/LIR, Atg8-family protein-interacting motif/LC3-interacting (pink); TM, (light blue); BH1-4, Bcl-2 1-4 (green green); PPlase, peptidyl-prolyl cis-trans isomerase (orange); TPR, tetratricopeptide (purple); CaM, calmodulin-binding (dark red). size indicated amino acids. (B-D) Models activation recruitment surface. (B), BNIP3, BCL2L13, FKBP8 (C), FUNDC1, NIX (D) bind ATG8 then machinery Phosphorylation dephosphorylation serve regulatory activity receptors. For details, see text. Several lines phosphorylation event Atg32-mediated 2B). During respiration shift starvation, phosphorylated manner dependent Atg11-interacting motif Ser114 Ser119 (Aoki 2011; Kondo-Okamoto 2012). Importantly, post-translational modification CK2, evolutionarily variety (Kanki 2013). interacts directly phosphorylates vitro Mutagenesis Ser114, Ser119, residues impairment destabilizes Atg32-Atg11 interactions strongly suppresses 2012; 2013), CK2-dependent could step activate recruiting recent study has demonstrated 2A (PP2A)-like Ppg1 critical negatively (Furukawa lacking Ppg1, even respiratory log (stage prior induction), likely resulting increased accelerate Ppg1-dependent suppression requires partners Far have previously been suggested pheromone-induced cycle arrest (Pracheil Liu, findings raise possibility Ppg1-Far dephosphorylates competing against CK2-mediated under non-inducing conditions. known proteolytically cleaved Yme1, catalytic subunit metalloprotease inner (IMM) belongs ATPases activities (AAA) (Leonhard 1996). Upon processed C-terminal portion Yme1-dependent (Wang 2013) Yme1 leads strong support idea Yme1-mediated proteolysis required efficient However, studies suggest minor no deficiencies (Welter 2013; Gaspard McMaster, 2015), raising processing relevant some strains ER factors connected contact sites ER–mitochondria encounter (ERMES) facilitates transfer (Kornmann ERMES discrete foci where closely positioned, loss severe defects starvation-induced (Bockler Westermann, 2014). component Mmm1 forms co-localize dot-like structures, Ubiquitylation Mdm12/34 Rsp5 linked (Belgareh-Touze regulated Get1/2 Opi3, (Sakakibara 2015; insertion tail-anchored (Schuldiner Schuldiner Wang causes slightly hardly affected (Onishi How trans remains unclear. Surprisingly, methyltransferase ER, induction Opi3 biosynthesis pathway conversion PC. Depletion aberrant elevation glutathione levels reduces thus affects (Deffieu Sakakibara respiring coordinate methylation through unknown mechanisms. mammals mammals, mechanistically than different signals developmental changes. Disruption potential potent trigger (Elmore 2001). CCCP, proton-selective ionophore, antimycin (an inhibitor III) commonly impair Because toxic induces non-physiological damage especially neurons, often induce neuronal (Cai Ashrafi Both reagents depolarization accumulation OMM. integral members (LC3A/B/C, GABARAP, GABARAP-L1/2) regions (LIRs) regulate membranes enclosing Two One group includes (also NIX) (Boyd 1994; Matsushima 1998; Chen 1999; Vande Velde 2000; Regula 2002; Kubli Schweers Hanna 2012), (Liu counterpart (Murakawa 2015) following part, namely FKBP (Bhujabal hypoxic (Zhang response upregulated anchored OMM (TM) exposing N-terminal cytosol (Hanna usually expressed inactive monomer cytosol, but signals, stable homodimer TM integrated (Chen 1997; Ray mutations, which disrupt homodimerization do not affect localization, cause defect, supporting Similar 2A) mutations block interaction LC3, defects. Ser17 Ser24 near BNIP3-LC3 (Zhu 2C). shows (53–56% acid sequence identity) (Matsushima 1999) reticulocyte nucleus, eliminated, so erythrocytes can keep maximum space hemoglobin (Koury Yoshida Fader Colombo, 2006). With similarity restore reticulocytes contains LC3A, LC3B, GABARAP-L1, GABARAP-L2 (Novak 2010) CCCP-treated cells, recruits GABARAP-L1 2010). Ser34 Ser35, tandem serine motif, stabilizes NIX-LC3 (Rogov 2017) 2D). dimerization NIX, region, (Marinkovic 2020). Accumulation (triggered phosphorylation) NIX-mediated LC3 (Melser phosphorylation, Rheb, small GTPase superfamily, translocates mitophagosome Expression HeLa respiration, decreases consumption capacity Whether phenotypes depend Rheb-induced addressed. shown inhibit crucial (Li 2007). As (Bartolome 2017), BNIP3-dependent inhibition might facilitate take part positive feedback loop amplify initiation signal reported PINK1/Parkin-mediated ubiquitylated Parkin, turn adaptor binds both LC3/GABARAP (Gao Parkin translocation 2016a). CCCP-induced depolarization, (Ding 2010b). Pathophysiological relevance Parkinson's disease unknown. hypoxia-induced It typical three domains 2012) Mutations FUNDC1-LC3 OMM-anchored ubiquitylate several acting dynamics (Yonashiro 2006; Sugiura Park decreased hypoxia ubiquitin–proteasome-dependent due MARCH5-mediated ubiquitylation Lys119 Knockdown endogenous MARCH5 mutant impairs enhancing Ser13 Tyr18 located motif. mediates becomes inactivated, causing Tyr18, stabilization promotion enhances Hypoxia (near motif) 2014b). variant defective inhibits normoxic BCL2L1/Bcl-xL, antiapoptotic BH3 molecule, PGAM5-FUNDC1 prevent 2014a). homologs far identified motifs morphology fragmentation, silencing elongation BCL2L13-dependent conventional Atg7, core essential lipidation second reduce absence notion seems contribute regulation BCL2L13-LC3 mutation Ser272 localize 2019). elucidated. immunosuppressant drug FK506 tacrolimus) transcription, folding/trafficking, apoptosis (Bonner Boulianne, Co-overexpression LC3A depolarized CCCP-treated, Parkin-depleted canonical N-terminus C-terminus preferentially over vivo, Moreover, escape degradation-prone localizes (Saita Bhujabal Given complexity versatile needed clarify whether involved Ubiquitin-mediated (PD) neurodegenerative characterized death dopaminergic neurons (Lotharius Brundin, 2002). PD occurs sporadically 1–2% people above 65 years age arise earlier genetic mutations. Common observed patients motor symptoms (tremor, bradykinesia, rigidity, postural instability) result substantia nigra. Non-motor autono

Язык: Английский

Процитировано

971

Autophagy in Human Diseases DOI
Noboru Mizushima, Beth Levine

New England Journal of Medicine, Год журнала: 2020, Номер 383(16), С. 1564 - 1576

Опубликована: Окт. 14, 2020

Autophagy is a complex process of intracellular degradation senescent or malfunctioning organelles. Dysregulated autophagy associated with certain cancers, neurodegenerative diseases, immune dysfunction, and aging. Therapies aimed at regulating are being developed.

Язык: Английский

Процитировано

867

Autophagy and autophagy-related pathways in cancer DOI Open Access
Jayanta Debnath, Noor Gammoh, Kevin M. Ryan

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(8), С. 560 - 575

Опубликована: Март 2, 2023

Язык: Английский

Процитировано

709

The mechanisms and roles of selective autophagy in mammals DOI
Jose Norberto S. Vargas, Maho Hamasaki, Tsuyoshi Kawabata

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 24(3), С. 167 - 185

Опубликована: Окт. 27, 2022

Язык: Английский

Процитировано

596

Targeted protein degradation: mechanisms, strategies and application DOI Creative Commons
Lin Zhao, Jia Zhao,

Kunhong Zhong

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 4, 2022

Abstract Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application activity modulators, particularly inhibitors, has been the mainstream in development. In recent years, PROteolysis TArgeting Chimeras (PROTAC) technology emerged as one most promising approaches to remove specific disease-associated proteins by exploiting cells’ own destruction machinery. addition PROTAC, many different targeted degradation (TPD) strategies including, but not limited to, molecular glue, Lysosome-Targeting Chimaera (LYTAC), Antibody-based PROTAC (AbTAC), are emerging. These technologies have only greatly expanded scope TPD, also provided fresh insights into discovery. Here, we summarize advances major TPD technologies, discuss their potential applications, hope provide a prime for both biologists chemists who interested this vibrant field.

Язык: Английский

Процитировано

446

Machinery, regulation and pathophysiological implications of autophagosome maturation DOI Open Access
Yan Zhao, Patrice Codogno, Hong Zhang

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2021, Номер 22(11), С. 733 - 750

Опубликована: Июль 23, 2021

Язык: Английский

Процитировано

391

Autophagy genes in biology and disease DOI Open Access
Hayashi Yamamoto, Sidi Zhang, Noboru Mizushima

и другие.

Nature Reviews Genetics, Год журнала: 2023, Номер 24(6), С. 382 - 400

Опубликована: Янв. 12, 2023

Язык: Английский

Процитировано

373

Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion DOI
Kazuaki Matoba, Tetsuya Kotani, Akihisa Tsutsumi

и другие.

Nature Structural & Molecular Biology, Год журнала: 2020, Номер 27(12), С. 1185 - 1193

Опубликована: Окт. 26, 2020

Язык: Английский

Процитировано

354

Mechanisms of Selective Autophagy DOI
Trond Lamark, Terje Johansen

Annual Review of Cell and Developmental Biology, Год журнала: 2021, Номер 37(1), С. 143 - 169

Опубликована: Июнь 21, 2021

Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through activity selective receptors (SARs). SARs interact with autophagy-related (ATG)8 family proteins via sequence motifs called LC3-interacting region (LIR) in vertebrates and Atg8-interacting (AIMs) yeast plants. can be divided two broad groups: soluble membrane bound. Cargo substrate selection may independent dependent ubiquitin labeling cargo. In this review, we discuss mechanisms mammalian a focus on unifying principles employed recognition, interaction forming autophagosome LIR-ATG8 interactions, recruitment core for efficient formation substrate.

Язык: Английский

Процитировано

290