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

Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation DOI Creative Commons
David Broadbent, Carlo Barnaba, Gloria I. Perez

и другие.

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

Опубликована: Апрель 28, 2023

Autophagy is a catabolic pathway required for the recycling of cytoplasmic materials. To define mechanisms underlying autophagy it critical to quantitatively characterize dynamic behavior factors in living cells. Using panel cell lines expressing HaloTagged from their endogenous loci, we analyzed abundance, single-molecule dynamics, and autophagosome association kinetics proteins involved biogenesis. We demonstrate that formation inefficient ATG2-mediated tethering donor membranes key commitment step formation. Furthermore, our observations support model phagophores are initiated by accumulation on mobile ATG9 vesicles, ULK1 complex PI3-kinase form positive feedback loop Finally, duration biogenesis ∼110 s. In total, work provides quantitative insight into establishes an experimental framework analyze human

Язык: Английский

Процитировано

50
The Role of ATG9 Vesicles in Autophagosome Biogenesis DOI Creative Commons
Elisabeth Holzer, Sascha Martens, Susanna Tulli

и другие.

Journal of Molecular Biology, Год журнала: 2024, Номер 436(15), С. 168489 - 168489

Опубликована: Фев. 10, 2024

Autophagy mediates the degradation and recycling of cellular material in lysosomal system. Dysfunctional autophagy is associated with a plethora diseases including uncontrolled infections, cancer neurodegeneration. In macroautophagy (hereafter autophagy) this encapsulated double membrane vesicles, autophagosomes, which form upon induction autophagy. The precursors to referred as phagophores, first appear small flattened cisternae, gradually enclose cargo they grow. assembly phagophores during initiation has been major subject investigation over past decades. A special focus ATG9, only conserved transmembrane protein among core machinery. majority ATG9 localizes Golgi-derived vesicles. Here we review recent advances breakthroughs regarding our understanding how vesicles it resides serve assemble machinery establish contact sites for autophagosome biogenesis. We also highlight open questions field that need be addressed years come.

Язык: Английский

Процитировано

24
ATG9A facilitates the closure of mammalian autophagosomes DOI
Ruheena Javed, Muriel Mari, Einar S Trosdal

и другие.

The Journal of Cell Biology, Год журнала: 2025, Номер 224(2)

Опубликована: Янв. 2, 2025

Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite its subsequent fusion with endolysosomal organelles and degradation sequestered cargo. ATG9A, key integral protein pathway, best known role in formation expansion phagophores. Here, we report hitherto unappreciated function mammalian ATG9A directing closure. partners IQGAP1 ESCRT-III component CHMP2A to facilitate this final stage formation. Thus, central hub governing all major aspects biogenesis, from unique ATG factor progressive functionalities affecting physiological outputs autophagy.

Язык: Английский

Процитировано

2
Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function DOI Creative Commons

Masroor Ahmad Paddar,

Fulong Wang, Einar S Trosdal

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Янв. 7, 2025

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number biological outputs includes control tuberculosis in animal models. Here, we show that associates retromer’s components VPS26, VPS29, and VPS35 modulates retromer function. Knockout blocked trafficking key glucose transporter sorted by retromer, GLUT1, to plasma membrane. Knockouts other genes essential for component, affected GLUT1 sorting, indicating atg8ylation process affects function endosomal sorting. The contribution sorting was independent canonical autophagy. These findings expand scope specific processes cell dependent on its known interactors.

Язык: Английский

Процитировано

2
ATG16L1 induces the formation of phagophore-like membrane cups DOI

Jagan Mohan,

Satish Babu Moparthi, Christine Girard-Blanc

и другие.

Nature Structural & Molecular Biology, Год журнала: 2024, Номер 31(9), С. 1448 - 1459

Опубликована: Июнь 4, 2024

Язык: Английский

Процитировано

13
Exploring the ATG9A interactome uncovers interaction with VPS13A DOI Creative Commons
Alexander R. van Vliet,

Harold B.J. Jefferies,

Peter Faull

и другие.

Journal of Cell Science, Год журнала: 2024, Номер 137(4)

Опубликована: Янв. 31, 2024

ATG9A, a transmembrane protein of the core autophagy pathway, cycles between Golgi, endosomes and vesicular compartment. ATG9A was recently shown to act as lipid scramblase, this function is thought require its interaction with another protein, ATG2A, which acts transfer protein. Together, ATG2A are proposed expand growing autophagosome. However, implicated in other pathways including membrane repair droplet homeostasis. To elucidate interactors within or beyond autophagy, we performed an interactome analysis through mass spectrometry. This revealed host proteins involved synthesis trafficking, ACSL3, VPS13A VPS13C. Furthermore, show that directly interacts forms complex distinct from ATG9A-ATG2A complex.

Язык: Английский

Процитировано

11
Structural basis for lipid transfer by the ATG2A–ATG9A complex DOI
Yang Wang, Selma Dahmane, Rujuan Ti

и другие.

Nature Structural & Molecular Biology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 22, 2024

Язык: Английский

Процитировано

10
Role of AMBRA1 in mitophagy regulation: emerging evidence in aging-related diseases DOI Creative Commons
Martina Di Rienzo, Alessandra Romagnoli, Giulia Refolo

и другие.

Autophagy, Год журнала: 2024, Номер 20(12), С. 2602 - 2615

Опубликована: Авг. 8, 2024

Aging is a gradual and irreversible physiological process that significantly increases the risks of developing variety pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, immune system diseases. Mitochondria are energy-producing organelles, their proper functioning crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release harmful reactive oxygen species (ROS) DNA, which leads to oxidative stress, inflammation damage, common features associated with various age-related pathologies. The impairment mitophagy, selective removal damaged or dysfunctional mitochondria by autophagy, relevant development progression molecular mechanisms regulates mitophagy levels in aging remain largely uncharacterized. AMBRA1 intrinsically disordered scaffold protein unique property regulating activity both proliferation autophagy core machineries. While role during embryonic neoplastic transformation has been extensively investigated, its functions post-mitotic cells adult tissues have limited due lethality caused deficiency. Recently, key selectively emerged. Here we summarize discuss these results aim providing comprehensive view roles AMBRA1, how defective functionally linked alterations observed degenerative disorders, muscular dystrophy/sarcopenia, Parkinson diseases, Alzheimer diseases macular degeneration.

Язык: Английский

Процитировано

9
The autophagy protein ATG-9 regulates lysosome function and integrity DOI

Kangfu Peng,

Guoxiu Zhao,

Hongyu Zhao

и другие.

The Journal of Cell Biology, Год журнала: 2025, Номер 224(6)

Опубликована: Апрель 9, 2025

The transmembrane autophagy protein ATG9 has multiple functions essential for autophagosome formation. Here, we uncovered a novel function of ATG-9 in regulating lysosome biogenesis and integrity Caenorhabditis elegans. Through genetic screen, identified that mutations attenuating the lipid scrambling activity suppress defect epg-5 mutants, which non-degradative autolysosomes accumulate. scramblase-attenuated mutants promote delivery lysosome-localized hydrolases also facilitate maintenance integrity. manipulation phospholipid levels, found reduction phosphatidylethanolamine (PE) suppresses defects damage associated with impaired lysosomal degradation. Our results reveal modulation composition distribution, e.g., by scramblase or reducing PE level, regulates

Язык: Английский

Процитировано

1
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

7