Antioxidative Role of Heterophagy, Autophagy, and Mitophagy in the Retina and Their Association with the Age-Related Macular Degeneration (AMD) Etiopathogenesis DOI Creative Commons
Małgorzata Nita, Andrzej Grzybowski

Antioxidants, Год журнала: 2023, Номер 12(7), С. 1368 - 1368

Опубликована: Июнь 29, 2023

Age-related macular degeneration (AMD), an oxidative stress-linked neurodegenerative disease, leads to irreversible damage of the central retina and severe visual impairment. Advanced age long-standing influence stress cellular play crucial roles in AMD etiopathogenesis. Many authors emphasize role heterophagy, autophagy, mitophagy maintaining homeostasis retina. Relevantly modifying activity both macroautophagy pathways represents one new therapeutic strategies AMD. Our review provides overview antioxidative presents associations between dysregulations these molecular mechanisms The performed extensive analysis literature, employing PubMed Google Scholar, complying with 2013–2023 period, using following keywords: age-related degeneration, RPE cells, reactive oxygen species, stress, mitophagy. Heterophagy, retina; however, they become sluggish dysregulated contribute development progression. In retina, also NFE2L2 PGC-1α proteins, NFE2L2/PGC-1α/ARE signaling cascade, Nrf2 factor, p62/SQSTM1/Keap1-Nrf2/ARE pathway, circulating miRNAs, Yttrium oxide nanoparticles experimentally animal studies.

Язык: Английский

The interplay between autophagy and cGAS-STING signaling and its implications for cancer DOI Creative Commons
Maximilian Schmid, Patrick D. Fischer, Magdalena Engl

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 10, 2024

Autophagy is an intracellular process that targets various cargos for degradation, including members of the cGAS-STING signaling cascade. senses cytosolic double-stranded DNA and triggers innate immune response through type I interferons. Emerging evidence suggests autophagy plays a crucial role in regulating fine-tuning signaling. Reciprocally, pathway can actively induce canonical as well non-canonical forms autophagy, establishing regulatory network feedback mechanisms alter both autophagic pathway. The crosstalk between impacts wide variety cellular processes such protection against pathogenic infections neurodegenerative disease, autoinflammatory disease cancer. Here we provide comprehensive overview involved signaling, with specific focus on interactions two pathways their importance

Язык: Английский

Процитировано

8
Autophagy in Its (Proper) Context: Molecular Basis, Biological Relevance, Pharmacological Modulation, and Lifestyle Medicine DOI Creative Commons
Miguel Á. Ortega, Oscar Fraile‐Martínez,

Diego De León-Oliva

и другие.

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(7), С. 2532 - 2554

Опубликована: Янв. 1, 2024

Autophagy plays a critical role in maintaining cellular homeostasis and responding to various stress conditions by the degradation of intracellular components.In this narrative review, we provide comprehensive overview autophagy's molecular basis, biological significance, pharmacological modulation, its relevance lifestyle medicine.We delve into intricate mechanisms that govern autophagy, including macroautophagy, microautophagy chaperone-mediated autophagy.Moreover, highlight significance autophagy aging, immunity, metabolism, apoptosis, tissue differentiation systemic diseases, such as neurodegenerative or cardiovascular diseases cancer.We also discuss latest advancements modulation their potential implications clinical settings.Finally, explore intimate connection between factors emphasizing how nutrition, exercise, sleep patterns environmental can significantly impact autophagic process.The integration medicine research opens new avenues for promoting health longevity through personalized interventions.

Язык: Английский

Процитировано

8
Toward a standard model for autophagosome biogenesis DOI Creative Commons
Annan SI Cook, James H. Hurley

The Journal of Cell Biology, Год журнала: 2023, Номер 222(7)

Опубликована: Июнь 5, 2023

Two papers in this issue resolve a long-standing obstacle to “standard model” for autophagosome biogenesis mammals. The first, Olivas et al. (2023. J. Cell Biol. https://doi.org/10.1083/jcb.202208088), uses biochemistry confirm that the lipid scramblase ATG9A is bona fide component, while second, Broadbent https://doi.org/10.1083/jcb.202210078), particle tracking show dynamics of autophagy proteins are consistent with concept.

Язык: Английский

Процитировано

16
The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy DOI Creative Commons
Xuan Zhao, Sisi Yang, Benjamin A. Clark

и другие.

PLoS Biology, Год журнала: 2023, Номер 21(4), С. e3002030 - e3002030

Опубликована: Апрель 13, 2023

Autophagy is essential for cellular homeostasis and function. In neurons, autophagosome biogenesis temporally spatially regulated to occur near presynaptic sites, in part via the trafficking of autophagy transmembrane protein ATG-9. The molecules that regulate by sorting ATG-9 at synapses remain largely unknown. Here, we conduct forward genetic screens single C. elegans neurons identify a role long isoform active zone Clarinet (CLA-1L) regulating synapses, autophagy. We determine disrupting CLA-1L results abnormal accumulation containing vesicles enriched with clathrin. phenotype cla-1(L) mutants not observed other synaptic vesicle proteins, suggesting distinct mechanisms ATG-9-containing vesicles. Through analyses, uncover adaptor complexes genetically interact CLA-1 sorting. also extends from periactive interacts proteins Our findings reveal novel roles

Язык: Английский

Процитировано

14
Autophagosome biogenesis and organelle homeostasis in plant cells DOI

Xiaohong Zhuang,

Baiying Li, Liwen Jiang

и другие.

The Plant Cell, Год журнала: 2024, Номер 36(9), С. 3009 - 3024

Опубликована: Март 27, 2024

Autophagy is one of the major highly inducible degradation processes in response to plant developmental and environmental signals. In different stimuli, cellular materials, including proteins organelles, can be sequestered into a double membrane autophagosome structure either selectively or nonselectively. The formation an as well its delivery vacuole involves complex dynamic processes. identification characterization conserved autophagy-related (ATG) their related regulators have greatly advanced our understanding molecular mechanism underlying biogenesis function cells. Autophagosome tightly regulated by coordination multiple ATG non-ATG selective cargo recruitment. This review updates current knowledge biogenesis, with special emphasis on core machinery that drives autophagosome-organelle interactions under abiotic stress conditions.

Язык: Английский

Процитировано

5
AMPK regulates phagophore-to-autophagosome maturation DOI Creative Commons
Carlo Barnaba, David Broadbent, E Kaminsky

и другие.

The Journal of Cell Biology, Год журнала: 2024, Номер 223(8)

Опубликована: Май 22, 2024

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach donor membranes, expand via ATG2-mediated transfer, capture cargo, and mature into autophagosomes, ultimately fusing lysosomes for their degradation. be activated by nutrient stress, example, a reduction in the levels amino acids. In contrast, how regulated low ATP AMP-activated kinase (AMPK), therapeutic target, less clear. Using live-cell imaging automated image analysis pipeline, we systematically dissect starvation regulates autophagosome biogenesis. We demonstrate glucose downregulates maturation AMPK-mediated inhibition phagophore tethering membrane. Our results clarify AMPKs regulatory role highlight its potential as target reduce autophagy.

Язык: Английский

Процитировано

5
Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology DOI Creative Commons
Ji-Young Choi,

Haeun Jang,

Xuan Zhao

и другие.

Autophagy, Год журнала: 2024, Номер 20(11), С. 2373 - 2387

Опубликована: Авг. 4, 2024

Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in year 2000 yeast. Two homologs of ATG9A and ATG9B, have been found mammals. While ATG9B shows a tissue-specific expression pattern, such as placenta pituitary gland, is ubiquitously expressed. Additionally, deficiency leads to severe defects not at molecular cellular levels but also organismal level, suggesting key fundamental roles for ATG9A. The subcellular localization on small vesicles its functional relevance autophagy suggested potential role lipid supply during autophagosome biogenesis. Nevertheless, precise autophagic process has remained long-standing mystery, especially neurons. Recent findings, however, including structural, proteomic, biochemical analyses, provided new insights into function expansion phagophore membrane. In this review, we aim understand various aspects ATG9 (in invertebrates plants)/ATG9A mammals), localization, trafficking, other functions, nonneuronal cells neurons by comparing recent discoveries related ATG9/ATG9A proposing directions future research.

Язык: Английский

Процитировано

5
ATG9 resides on a unique population of small vesicles in presynaptic nerve terminals DOI Creative Commons
Beyenech Binotti, Momchil Ninov, Andreia P. Cepeda

и другие.

Autophagy, Год журнала: 2023, Номер 20(4), С. 883 - 901

Опубликована: Окт. 26, 2023

In neurons, autophagosome biogenesis occurs mainly in distal axons, followed by maturation during retrograde transport. Autophagosomal growth depends on the supply of membrane lipids which requires small vesicles containing ATG9, a lipid scramblase essential for macroautophagy/autophagy. Here, we show that ATG9-containing are enriched synapses and resemble synaptic size density. The proteome immuno-isolated from nerve terminals showed conspicuously low levels trafficking proteins except AP2-complex some enzymes involved endosomal phosphatidylinositol metabolism. Super resolution microscopy isolated revealed represent distinct vesicle population with limited overlap not only but also other membranes secretory pathway, uncovering surprising heterogeneity their composition. Our results compatible view function as shuttles scavenge various intracellular to support biogenesis.

Язык: Английский

Процитировано

13
The ULK1 effector BAG2 regulates autophagy initiation by modulating AMBRA1 localization DOI Creative Commons
Devanarayanan Siva Sankar, Stéphanie Pébernard,

Christine Vionnet

и другие.

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114689 - 114689

Опубликована: Авг. 27, 2024

Autophagy initiation is regulated by the ULK1 kinase complex. To gain insights into functions of holo-complex, we generated a deep interactome combining affinity purification- and proximity labeling-mass spectrometry all four complex members: ULK1, ATG13, ATG101, RB1CC1/FIP200. Under starvation conditions, interacts with several protein lipid kinases phosphatases, implying formation signalosome. Interestingly, selective autophagy receptors also interact indicating activation pathways nutrient starvation. One effector HSC/HSP70 co-chaperone BAG2, which regulates subcellular localization VPS34 member AMBRA1. Depending on nutritional status, BAG2 has opposing roles. In growth unphosphorylated form sequesters AMBRA1, attenuating induction. phosphorylates Ser31, supports recruitment AMBRA1 to ER membrane, positively affecting autophagy.

Язык: Английский

Процитировано

4
Trafficking of K63-polyubiquitin modified membrane proteins in a macroautophagy-independent pathway is linked to ATG9A DOI Open Access
Francesco Scavone,

Sharon Lian,

Eeva‐Liisa Eskelinen

и другие.

Molecular Biology of the Cell, Год журнала: 2025, Номер 36(4)

Опубликована: Фев. 19, 2025

Cytoplasmic K63-linked polyubiquitin signals have well-established roles in endocytosis and selective autophagy. However, how these help to direct different cargos intracellular trafficking routes is unclear. Here we report that, when the K63-polyubiquitin signal blocked by expression of a high-affinity sensor (named Vx3), many proteins originating from plasma membrane are found trapped clusters small vesicles that colocalize with ATG9A, transmembrane protein plays an essential role Importantly, whereas ATG9A required for cluster formation, other core autophagy machinery as well cargo receptors not required. Although sequestered vesicular ATG9-dependent manner, additional needed induce LC3 conjugation. Upon removal Vx3 block, K63-polyubiquitylated rapidly delivered lysosomes. These observations suggest unexpected K63-polyubiquitin–modified proteins.

Язык: Английский

Процитировано

0