Autophagy Reports, Journal Year: 2024, Volume and Issue: 3(1)
Published: Oct. 23, 2024
is a ubiquitous protozoan parasite that can reside long-term within hosts as intracellular tissue cysts comprised of chronic stage bradyzoites. To perturb infection requires better understanding the cellular processes mediate persistence. Macroautophagy/autophagy catabolic and homeostatic pathway required for
Language: Английский
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
24
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
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
The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(22)
Published: Aug. 25, 2023
Nix is a membrane-anchored outer mitochondrial protein that induces mitophagy. While has an LC3-interacting (LIR) motif binds to ATG8 proteins, it also contains minimal essential region (MER) mitophagy through unknown mechanism. We used chemically induced dimerization (CID) probe the mechanism of Nix-mediated and found both LIR MER are required for robust find interacts with autophagy effector WIPI2 recruits mitochondria. The converts homogeneous distribution on surface mitochondria into puncta, even in absence ATG8s. Together, this work reveals unanticipated mechanisms Nix-induced elusive role MER, while describing interesting example induction acts downstream canonical initiation complexes.
Language: Английский
Citations
23
The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(5)
Published: Feb. 6, 2024
Axonal transport is essential for neuronal survival. This driven by microtubule motors including dynein, which transports cargo from the axon tip back to cell body. function requires its cofactor dynactin and regulators LIS1 NDEL1. Due difficulties imaging dynein at a single-molecule level, it unclear how this motor coordinate along length of axon. Here, we use neuron-inducible human stem line (NGN2-OPTi-OX) endogenously tag components visualize them near-single molecule regime. In retrograde direction, find that can move entire (>500 µm). Furthermore, NDEL1 also undergo long-distance movement, despite being mainly implicated with initiation transport. Intriguingly, in anterograde dynein/LIS1 moves faster than dynactin/NDEL1, consistent on different cargos. Therefore, neurons ensure efficient holding dynein/dynactin cargos over long distances but keeping separate until required.
Language: Английский
Citations
11
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
8
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: April 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
Language: Английский
Citations
7
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Aug. 21, 2024
Abstract Autophagy is a highly conserved process from yeast to mammals in which intracellular materials are engulfed by double-membrane organelle called autophagosome and degrading fusing with the lysosome. The of autophagy regulated sequential recruitment function autophagy-related (Atg) proteins. Genetic hierarchical analyses show that ULK1 complex comprised ULK1-FIP200-ATG13-ATG101 translocating cytosol formation sites as most upstream ATG factor; this translocation critical initiation. However, how occurs remains unclear. Here, we palmitoylated palmitoyltransferase ZDHHC13 translocated site upon induction. We find palmitoylation required for Moreover, enhances phosphorylation ATG14L, activating PI3-Kinase producing phosphatidylinositol 3-phosphate, one membrane’s lipids. Our results reveal translocates during autophagy.
Language: Английский
Citations
7
The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(7)
Published: June 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.
Language: Английский
Citations
16
The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(8)
Published: May 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.
Language: Английский
Citations
5