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1.
J Clin Invest ; 133(8)2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37066873

RESUMO

Cancer cells rely on lysosome-dependent degradation to recycle nutrients that serve their energetic and biosynthetic needs. Despite great interest in repurposing the antimalarial hydroxychloroquine as a lysosomal inhibitor in clinical oncology trials, the mechanisms by which hydroxychloroquine and other lysosomal inhibitors induce tumor-cell cytotoxicity remain unclear. In this issue of the JCI, Bhardwaj et al. demonstrate that DC661, a dimeric form of chloroquine that inhibits palmitoyl-protein thioesterase 1 (PPT1), promoted lysosomal lipid peroxidation, resulting in lysosomal membrane permeabilization and tumor cell death. Remarkably, this lysosomal cell death pathway elicited cell-intrinsic immunogenicity and promoted T lymphocyte-mediated tumor cell clearance. The findings provide the mechanistic foundation for the potential combined use of immunotherapy and lysosomal inhibition in clinical trials.


Assuntos
Hidroxicloroquina , Neoplasias , Humanos , Hidroxicloroquina/metabolismo , Peroxidação de Lipídeos , Morte Celular Imunogênica , Cloroquina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Lisossomos/metabolismo
2.
Nat Rev Mol Cell Biol ; 24(8): 560-575, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36864290

RESUMO

Maintenance of protein homeostasis and organelle integrity and function is critical for cellular homeostasis and cell viability. Autophagy is the principal mechanism that mediates the delivery of various cellular cargoes to lysosomes for degradation and recycling. A myriad of studies demonstrate important protective roles for autophagy against disease. However, in cancer, seemingly opposing roles of autophagy are observed in the prevention of early tumour development versus the maintenance and metabolic adaptation of established and metastasizing tumours. Recent studies have addressed not only the tumour cell intrinsic functions of autophagy, but also the roles of autophagy in the tumour microenvironment and associated immune cells. In addition, various autophagy-related pathways have been described, which are distinct from classical autophagy, that utilize parts of the autophagic machinery and can potentially contribute to malignant disease. Growing evidence on how autophagy and related processes affect cancer development and progression has helped guide efforts to design anticancer treatments based on inhibition or promotion of autophagy. In this Review, we discuss and dissect these different functions of autophagy and autophagy-related processes during tumour development, maintenance and progression. We outline recent findings regarding the role of these processes in both the tumour cells and the tumour microenvironment and describe advances in therapy aimed at autophagy processes in cancer.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Autofagia/fisiologia , Lisossomos , Microambiente Tumoral
3.
Autophagy ; 19(4): 1049-1054, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36628432

RESUMO

In this editors' corner, the section editors were asked to indicate where they see the autophagy field heading and to suggest what they consider to be key unanswered questions in their specialty area.


Assuntos
Autofagia , Pesquisa Biomédica , Pesquisa Biomédica/tendências
4.
Autophagy ; 19(5): 1551-1561, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36286616

RESUMO

LC3-dependent EV loading and secretion (LDELS) is a secretory autophagy pathway in which the macroautophagy/autophagy machinery facilitates the packaging of cytosolic cargos, such as RNA-binding proteins, into extracellular vesicles (EVs) for secretion outside of the cell. Here, we identify TFRC (transferrin receptor), one of the first proteins found to be secreted via EVs, as a transmembrane cargo of the LDELS pathway. Similar to other LDELS targets, TFRC secretion via EVs genetically requires components of the MAP1LC3/LC3-conjugation machinery but is independent of other ATGs involved in classical autophagosome formation. Furthermore, the packaging and secretion of this transmembrane protein into EVs depends on multiple ESCRT pathway components and the small GTPase RAB27A. Based on these results, we propose that the LDELS pathway promotes TFRC incorporation into EVs and its secretion outside the cell.Abbreviations: ATG: autophagy related; ESCRT: endosomal sorting complexes required for transport; EV: extracellular vesicle; EVP: extracellular vesicle and particle; ILV: intralumenal vesicle; LDELS: LC3-dependent EV loading and secretion; LIR: LC3-interacting region; MVE: multivesicular endosome; RBP: RNA-binding protein; TMT: tandem mass tag; TFRC: transferrin receptor.


Assuntos
Autofagia , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Endossomos/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Receptores da Transferrina/metabolismo
5.
Autophagy ; 18(10): 2498-2499, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35786367

RESUMO

Both macroautophagy/autophagy and extracellular vesicle (EV) secretion pathways converge upon the endolysosome system. Although lysosome impairment leads to defects in autophagic degradation, the impact of such dysfunction on EV secretion remains poorly understood. Recently, we uncovered a novel secretory autophagy pathway that employs EVs and nanoparticles (EVPs) for the secretion of autophagy cargo receptors outside the cell when either autophagosome maturation or lysosomal function is blocked. We term this process secretory autophagy during lysosome inhibition (SALI). SALI functionally requires multiple steps in classical autophagosome formation and the small GTPase RAB27A. Because the intracellular accumulation of autophagy cargo receptors perturbs cell signaling and quality control pathways, we propose that SALI functions as a failsafe mechanism to preserve protein and cellular homeostasis when autophagic or lysosomal degradation is impaired.


Assuntos
Autofagia , Proteínas Monoméricas de Ligação ao GTP , Autofagia/fisiologia , Endossomos/metabolismo , Lisossomos/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Via Secretória
7.
Proc Natl Acad Sci U S A ; 119(21): e2202016119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35537042

RESUMO

Autophagy defects are a risk factor for inflammatory bowel diseases (IBDs) through unknown mechanisms. Whole-body conditional deletion of autophagy-related gene (Atg) Atg7 in adult mice (Atg7Δ/Δ) causes tissue damage and death within 3 mo due to neurodegeneration without substantial effect on intestine. In contrast, we report here that whole-body conditional deletion of other essential Atg genes Atg5 or Fip200/Atg17 in adult mice (Atg5Δ/Δ or Fip200Δ/Δ) caused death within 5 d due to rapid autophagy inhibition, elimination of ileum stem cells, and loss of barrier function. Atg5Δ/Δ mice lost PDGFRα+ mesenchymal cells (PMCs) and Wnt signaling essential for stem cell renewal, which were partially rescued by exogenous Wnt. Matrix-assisted laser desorption ionization coupled to mass spectrometry imaging (MALDI-MSI) of Atg5Δ/Δ ileum revealed depletion of aspartate and nucleotides, consistent with metabolic insufficiency underlying PMC loss. The difference in the autophagy gene knockout phenotypes is likely due to distinct kinetics of autophagy loss, as deletion of Atg5 more gradually extended lifespan phenocopying deletion of Atg7 or Atg12. Thus, autophagy is required for PMC metabolism and ileum stem cell and mammalian survival. Failure to maintain PMCs through autophagy may therefore contribute to IBD.


Assuntos
Autofagia , Intestinos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Células-Tronco , Animais , Autofagia/genética , Proteína 5 Relacionada à Autofagia , Proteína 7 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Sobrevivência Celular , Camundongos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/metabolismo
8.
J Cell Biol ; 221(6)2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35446347

RESUMO

The endolysosome system plays central roles in both autophagic degradation and secretory pathways, including the release of extracellular vesicles and particles (EVPs). Although previous work reveals important interconnections between autophagy and EVP-mediated secretion, our understanding of these secretory events during endolysosome inhibition remains incomplete. Here, we delineate a secretory autophagy pathway upregulated in response to endolysosomal inhibition, which mediates EVP-associated release of autophagic cargo receptors, including p62/SQSTM1. This secretion is highly regulated and dependent on multiple ATGs required for autophagosome formation, as well as the small GTPase Rab27a. Furthermore, disrupting autophagosome maturation, either via genetic inhibition of autophagosome-to-autolysosome fusion or expression of SARS-CoV-2 ORF3a, is sufficient to induce EVP secretion of autophagy cargo receptors. Finally, ATG-dependent EVP secretion buffers against the intracellular accumulation of autophagy cargo receptors when classical autophagic degradation is impaired. Thus, we propose secretory autophagy via EVPs functions as an alternate route to clear sequestered material and maintain proteostasis during endolysosomal dysfunction or impaired autophagosome maturation.


Assuntos
Autofagia , Vesículas Extracelulares , Lisossomos , Proteostase , Autofagossomos/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Lisossomos/metabolismo , SARS-CoV-2 , Proteína Sequestossoma-1 , Proteínas Viroporinas , Proteínas rab27 de Ligação ao GTP
9.
Artigo em Inglês | MEDLINE | ID: mdl-35270256

RESUMO

The conventional paper-based system for malaria surveillance is time-consuming, difficult to track and resource-intensive. Few digital platforms are in use but wide-scale deployment and acceptability remain to be seen. To address this issue, we created a malaria surveillance mobile app that offers real-time data to stakeholders and establishes a centralised data repository. The MoSQuIT app was designed to collect data from the field and was integrated with a web-based platform for data integration and analysis. The MoSQuIT app was deployed on mobile phones of accredited social health activists (ASHA) working in international border villages in the northeast (NE) Indian states of Assam, Tripura and Arunachal Pradesh for 20 months in a phased manner. This paper shares the challenges and opportunities associated with the use of MoSQuIT for malaria surveillance. MoSQuIT employs the same data entry formats as the NVBDCP's malaria surveillance programme. Using this app, a total of 8221 fever cases were recorded, which included 1192 (14.5%) cases of P. falciparum malaria, 280 (3.4%) cases of P. vivax malaria and 52 (0.6%) mixed infection cases. Depending on network availability, GPS coordinates of the fever cases were acquired by the app. The present study demonstrated that mobile-phone-based malaria surveillance facilitates the quick transmission of data from the field to decision makers. Geospatial tagging of cases helped with easy visualisation of the case distribution for the identification of malaria-prone areas and potential outbreaks, especially in hilly and remote regions of Northeast India. However, to achieve the full operational potential of the system, operational challenges have to be overcome.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Aplicativos Móveis , Telemedicina , Febre , Humanos , Índia/epidemiologia , Malária/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia
10.
JMIR Form Res ; 5(11): e28951, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757321

RESUMO

BACKGROUND: A surveillance system is the foundation for disease prevention and control. Malaria surveillance is crucial for tracking regional and temporal patterns in disease incidence, assisting in recorded details, timely reporting, and frequency of analysis. OBJECTIVE: In this study, we aim to develop an integrated surveillance graphical app called FeverTracker, which has been designed to assist the community and health care workers in digital surveillance and thereby contribute toward malaria control and elimination. METHODS: FeverTracker uses a geographic information system and is linked to a web app with automated data digitization, SMS text messaging, and advisory instructions, thereby allowing immediate notification of individual cases to district and state health authorities in real time. RESULTS: The use of FeverTracker for malaria surveillance is evident, given the archaic paper-based surveillance tools used currently. The use of the app in 19 tribal villages of the Dhalai district in Tripura, India, assisted in the surveillance of 1880 suspected malaria patients and confirmed malaria infection in 93.4% (114/122; Plasmodium falciparum), 4.9% (6/122; P vivax), and 1.6% (2/122; P falciparum/P vivax mixed infection) of cases. Digital tools such as FeverTracker will be critical in integrating disease surveillance, and they offer instant data digitization for downstream processing. CONCLUSIONS: The use of this technology in health care and research will strengthen the ongoing efforts to eliminate malaria. Moreover, FeverTracker provides a modifiable template for deployment in other disease systems.

11.
Pathogens ; 10(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684207

RESUMO

With India aiming to achieve malaria elimination by 2030, several strategies have been put in place. With that aim, mass surveillance is now being conducted in some malaria-endemic pockets. As dry season mass surveillance has been shown to have its importance in targeting the reservoir, a study was undertaken to assess the parasite load by a sensitive molecular method during one of the mass surveys conducted in the dry winter period. It was executed in two malaria-endemic villages of Dhalai District, Tripura, in northeast India, also reported as P. falciparum predominated area. The present study found an enormous burden of Rapid Diagnostic Test negative malaria cases with P. vivax along with P. vivax and P. falciparum mixed infections during the mass surveillance from febrile and afebrile cases in dry winter months (February 2021-March 2021). Of the total 150 samples tested, 72 (48%) were positive and 78 (52%) negative for malaria by PCR. Out of the 72 positives, 6 (8.33%) were P. falciparum, 40 (55.55%) P. vivax, and 26 (36.11%) mixed infections. Out of 78 malaria negative samples, 6 (7.7%) were with symptoms, while among the total malaria positive, 72 cases 7 (9.8%) were with symptoms, and 65 (90.2%) were asymptomatic. Out of 114 samples tested by both microscopy and PCR, 42 samples turned out to be submicroscopic with 4 P. falciparum, 23 P. vivax, and 15 mixed infections. Although all P. vivax submicroscopic infections were asymptomatic, three P. falciparum cases were found to be febrile. Evidence of malaria transmission was also found in the vectors in the winter month. The study ascertained the use of molecular diagnostic techniques in detecting the actual burden of malaria, especially of P. vivax, in mass surveys. As Jhum cultivators in Tripura are at high risk, screening for the malarial reservoirs in pre-Jhum months can help with malaria control and elimination.

12.
Biol Open ; 10(10)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34533192

RESUMO

There is great interest in understanding the cellular mechanisms controlling autophagy, a tightly regulated catabolic and stress-response pathway. Prior work has uncovered links between autophagy and the Golgi reassembly stacking protein of 55 kDa (GRASP55), but their precise interrelationship remains unclear. Intriguingly, both autophagy and GRASP55 have been functionally and spatially linked to the endoplasmic reticulum (ER)---Golgi interface, broaching this compartment as a site where GRASP55 and autophagy may intersect. Here, we uncover that loss of GRASP55 enhances LC3 puncta formation, indicating that GRASP55 restricts autophagosome formation. Additionally, using proximity-dependent biotinylation, we identify a GRASP55 proximal interactome highly associated with the ER-Golgi interface. Both nutrient starvation and loss of GRASP55 are associated with coalescence of early secretory pathway markers. In light of these findings, we propose that GRASP55 regulates spatial organization of the ER-Golgi interface, which suppresses early autophagosome formation.


Assuntos
Autofagossomos/genética , Autofagia/genética , Retículo Endoplasmático/metabolismo , Proteínas da Matriz do Complexo de Golgi/metabolismo , Transdução de Sinais/genética , Humanos
13.
Autophagy ; 17(12): 4497-4498, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34470579

RESUMO

Growing evidence demonstrates that macroautophagy/autophagy in the host stroma influences the tumor microenvironment. We have uncovered that autophagy in host stromal fibroblasts is compulsory to initiate and maintain the desmoplastic fibrotic response that fosters mammary tumor progression. Genetic loss of fibroblast autophagy impedes COL1A/type 1 collagen secretion, which is required for the development of a stiff tissue matrix permissive for mammary tumor growth. As a result, stromal fibroblast autophagy deficiency impairs mammary tumor progression in vivo, even when the cancer cells themselves remain autophagy competent. Our results provide unique conceptual insight into how the autophagy pathway can be modulated to abolish the desmoplastic response required for cancer progression.


Assuntos
Autofagia , Neoplasias da Mama , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Fibroblastos/metabolismo , Humanos , Células Estromais/metabolismo , Microambiente Tumoral
14.
Sci Adv ; 7(32)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34362731

RESUMO

Altered mitochondrial quality control and dynamics may contribute to neurodegenerative diseases, including Parkinson's disease, but we understand little about these processes in neurons. We combined time-lapse microscopy and correlative light and electron microscopy to track individual mitochondria in neurons lacking the fission-promoting protein dynamin-related protein 1 (Drp1) and delineate the kinetics of PINK1-dependent pathways of mitochondrial quality control. Depolarized mitochondria recruit Parkin to the outer mitochondrial membrane, triggering autophagosome formation, rapid lysosomal fusion, and Parkin redistribution. Unexpectedly, these mitolysosomes are dynamic and persist for hours. Some are engulfed by healthy mitochondria, and others are deacidified before bursting. In other cases, Parkin is directly recruited to the matrix of polarized mitochondria. Loss of PINK1 blocks Parkin recruitment, causes LC3 accumulation within mitochondria, and exacerbates Drp1KO toxicity to dopamine neurons. These results define a distinct neuronal mitochondrial life cycle, revealing potential mechanisms of mitochondrial recycling and signaling relevant to neurodegeneration.

15.
Genes Dev ; 35(13-14): 963-975, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34168038

RESUMO

Autophagy inhibitors are currently being evaluated in clinical trials for the treatment of diverse cancers, largely due to their ability to impede tumor cell survival and metabolic adaptation. More recently, there is growing interest in whether and how modulating autophagy in the host stroma influences tumorigenesis. Fibroblasts play prominent roles in cancer initiation and progression, including depositing type 1 collagen and other extracellular matrix (ECM) components, thereby stiffening the surrounding tissue to enhance tumor cell proliferation and survival, as well as secreting cytokines that modulate angiogenesis and the immune microenvironment. This constellation of phenotypes, pathologically termed desmoplasia, heralds poor prognosis and reduces patient survival. Using mouse mammary cancer models and syngeneic transplantation assays, we demonstrate that genetic ablation of stromal fibroblast autophagy significantly impedes fundamental elements of the stromal desmoplastic response, including collagen and proinflammatory cytokine secretion, extracellular matrix stiffening, and neoangiogenesis. As a result, autophagy in stromal fibroblasts is required for mammary tumor growth in vivo, even when the cancer cells themselves remain autophagy-competent . We propose the efficacy of autophagy inhibition is shaped by this ability of host stromal fibroblast autophagy to support tumor desmoplasia.


Assuntos
Células Estromais , Microambiente Tumoral , Animais , Autofagia/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Fibroblastos/metabolismo , Humanos , Camundongos , Microambiente Tumoral/genética
16.
J Cell Sci ; 134(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34096604

RESUMO

In Saccharomyces cerevisiae, the selective autophagic degradation of mitochondria, termed mitophagy, is critically regulated by the adapter protein Atg32. Despite our knowledge about the molecular mechanisms by which Atg32 controls mitophagy, its physiological roles in yeast survival and fitness remains less clear. Here, we demonstrate a requirement for Atg32 in promoting spermidine production during respiratory growth and heat-induced mitochondrial stress. During respiratory growth, mitophagy-deficient yeast exhibit profound heat-stress induced defects in growth and viability due to impaired biosynthesis of spermidine and its biosynthetic precursor S-adenosyl methionine. Moreover, spermidine production is crucial for the induction of cytoprotective nitric oxide (NO) during heat stress. Hence, the re-addition of spermidine to Atg32 mutant yeast is sufficient to both enhance NO production and restore respiratory growth during heat stress. Our findings uncover a previously unrecognized physiological role for yeast mitophagy in spermidine metabolism and illuminate new interconnections between mitophagy, polyamine biosynthesis and NO signaling.


Assuntos
Mitofagia , Proteínas de Saccharomyces cerevisiae , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Resposta ao Choque Térmico/genética , Óxido Nítrico , Receptores Citoplasmáticos e Nucleares , Proteínas de Saccharomyces cerevisiae/genética , Espermidina
17.
Cancer Cell ; 39(5): 596-598, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33974856

RESUMO

Su et al. demonstrate that upon inhibiting autophagy, an intracellular nutrient recycling pathway, pancreatic ductal adenocarcinoma cells upregulate NRF2-mediated transcription of macropinocytosis pathway components, thereby triggering an alternate route for tumors to scavenge nutrients from extracellular sources. Accordingly, the combined inhibition of autophagy and macropinocytosis may improve cancer treatment.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Autofagia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Humanos , Fator 2 Relacionado a NF-E2/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Pinocitose
18.
FASEB Bioadv ; 3(5): 377-386, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33977236

RESUMO

Autophagy classically functions to maintain cell health during stressful conditions by targeting cytosolic components for degradation and recycling via lysosomal pathways. However, accumulating evidence also supports roles for autophagy-related genes (ATGs) in non-degradative processes including cellular secretion. Here, we review emerging roles for the autophagy machinery in regulating extracellular vesicle loading and secretion and discuss how functional coupling of these pathways may impact normal physiology and disease.

19.
Cell ; 184(10): 2649-2664.e18, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848463

RESUMO

Receptor tyrosine kinase (RTK)-mediated activation of downstream effector pathways such as the RAS GTPase/MAP kinase (MAPK) signaling cascade is thought to occur exclusively from lipid membrane compartments in mammalian cells. Here, we uncover a membraneless, protein granule-based subcellular structure that can organize RTK/RAS/MAPK signaling in cancer. Chimeric (fusion) oncoproteins involving certain RTKs including ALK and RET undergo de novo higher-order assembly into membraneless cytoplasmic protein granules that actively signal. These pathogenic biomolecular condensates locally concentrate the RAS activating complex GRB2/SOS1 and activate RAS in a lipid membrane-independent manner. RTK protein granule formation is critical for oncogenic RAS/MAPK signaling output in these cells. We identify a set of protein granule components and establish structural rules that define the formation of membraneless protein granules by RTK oncoproteins. Our findings reveal membraneless, higher-order cytoplasmic protein assembly as a distinct subcellular platform for organizing oncogenic RTK and RAS signaling.


Assuntos
Condensados Biomoleculares/metabolismo , Grânulos Citoplasmáticos/metabolismo , Neoplasias/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Proteínas ras/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Ativação Enzimática , Proteína Adaptadora GRB2/genética , Proteína Adaptadora GRB2/metabolismo , Células HEK293 , Humanos , Proteína SOS1/metabolismo , Transdução de Sinais
20.
Trends Biochem Sci ; 46(8): 673-686, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558127

RESUMO

The ATG8 family proteins are critical players in autophagy, a cytoprotective process that mediates degradation of cytosolic cargo. During autophagy, ATG8s conjugate to autophagosome membranes to facilitate cargo recruitment, autophagosome biogenesis, transport, and fusion with lysosomes, for cargo degradation. In addition to these canonical functions, recent reports demonstrate that ATG8s are also delivered to single-membrane organelles, which leads to highly divergent degradative or secretory fates, vesicle maturation, and cargo specification. The association of ATG8s with different vesicles involves complex regulatory mechanisms still to be fully elucidated. Whether individual ATG8 family members play unique canonical or non-canonical roles, also remains unclear. This review summarizes the many open molecular questions regarding ATG8s that are only beginning to be unraveled.


Assuntos
Autofagia , Proteínas Associadas aos Microtúbulos , Autofagossomos , Família da Proteína 8 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Lisossomos
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