Dynein and dynactin move long-range but are delivered separately to the axon tip DOI Creative Commons
Alexander D. Fellows, Michaela Bruntraeger, Thomas Burgold

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 3, 2023

Abstract 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-celllines (NGN2-OPTi-OX) endogenously tag components visualise them near-single molecule regime. In retrograde direction, find that can move entire (>500 μ m) in one go. Furthermore, NDEL1 also undergo longdistance movement, despite being mainly implicated with initiation transport. Intriguingly, anterograde dynein/LIS1 faster than dynactin/NDEL1 consistent on different cargos. Therefore, neurons ensure efficient holding dynein/dynactin cargos over long distances, but keeping separate until required.

Язык: Английский

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
Nix interacts with WIPI2 to induce mitophagy DOI Creative Commons
Eric Bunker, François Le Guerroué, Chunxin Wang

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(22)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

24
Dynein and dynactin move long-range but are delivered separately to the axon tip DOI Creative Commons
Alexander D. Fellows, Michaela Bruntraeger, Thomas Burgold

и другие.

The Journal of Cell Biology, Год журнала: 2024, Номер 223(5)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

13
Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy DOI Creative Commons
Keisuke Tabata, Kenta Imai,

Koki Fukuda

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

11
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

10
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
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

2
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
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