MicroRNAs regulating autophagy: opportunities in treating neurodegenerative diseases DOI Creative Commons
Morvarid Mohseni, Ghazal Behzad, Arezoo Farhadi

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Nov. 8, 2024

Neurodegenerative diseases (NDs) are increasingly prevalent in our aging population, imposing significant social and economic burdens. Currently, most ND patients receive only symptomatic treatment due to limited understanding of their underlying causes. Consequently, there is a pressing need for comprehensive research into the pathological mechanisms NDs by both researchers clinicians. Autophagy, cellular mechanism responsible maintaining equilibrium removing dysfunctional organelles misfolded proteins, plays vital role cell health implicated various diseases. MicroRNAs (miRNAs) exert influence on autophagy hold promise treating these These small oligonucleotides bind 3'-untranslated region (UTR) target mRNAs, leading mRNA silencing, degradation, or translation blockade. This review explores recent findings regulation autophagy-related genes different miRNAs conditions, including neurodegeneration inflammation-related The recognition as key regulators human has spurred investigations pharmacological compounds traditional medicines targeting disease models. catalyzed new wave therapeutic interventions aimed at modulating autophagy.

Language: 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

et al.

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(7)

Published: April 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

Language: Английский

Citations

53
The Role of ATG9 Vesicles in Autophagosome Biogenesis DOI Creative Commons
Elisabeth Holzer, Sascha Martens, Susanna Tulli

et al.

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(15), P. 168489 - 168489

Published: Feb. 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.

Language: Английский

Citations

29
ATG16L1 induces the formation of phagophore-like membrane cups DOI

Jagan Mohan,

Satish Babu Moparthi, Christine Girard-Blanc

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(9), P. 1448 - 1459

Published: June 4, 2024

Language: Английский

Citations

14
Exploring the ATG9A interactome uncovers interaction with VPS13A DOI Creative Commons
Alexander R. van Vliet,

Harold B.J. Jefferies,

Peter Faull

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(4)

Published: Jan. 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.

Language: Английский

Citations

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

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Language: Английский

Citations

11
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

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(7), P. 2532 - 2554

Published: Jan. 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.

Language: Английский

Citations

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

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(12), P. 2602 - 2615

Published: Aug. 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.

Language: Английский

Citations

10
ATG9A facilitates the closure of mammalian autophagosomes DOI
Ruheena Javed, Muriel Mari, Einar S Trosdal

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(2)

Published: Jan. 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.

Language: Английский

Citations

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

Masroor Ahmad Paddar,

Fulong Wang, Einar S Trosdal

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 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.

Language: Английский

Citations

2
Quiescent cell re-entry is limited by macroautophagy-induced lysosomal damage DOI
Andrew Murley,

Ann Catherine Popovici,

Xiaozhou Hu

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

2