Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

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Lysosomes drive the piecemeal removal of mitochondrial inner membrane

Nature, Journal Year: 2024, Volume and Issue: 632(8027), P. 1110 - 1117

Published: Aug. 21, 2024

Language: Английский

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Endocytosis blocks the vesicular secretion of exosome marker proteins

Science Advances, Journal Year: 2024, Volume and Issue: 10(19)

Published: May 8, 2024

Exosomes are secreted vesicles of ~30 to 150 nm diameter that play important roles in human health and disease. To better understand how cells release these vesicles, we examined the biogenesis most highly enriched exosome marker proteins, exosomal tetraspanins CD81, CD9, CD63. We show here endocytosis inhibits their vesicular secretion and, case CD9 triggers destruction. Furthermore, syntenin, a previously described factor, drives CD63 by blocking other inhibitors also induce plasma membrane accumulation Finally, is an expression-dependent inhibitor lysosomal proteins clathrin adaptor AP-2 mu2. These results suggest exosome-sized occurs primarily endocytosis-independent pathway.

Language: Английский

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Breaking barriers in targeted Therapy: Advancing exosome Isolation, Engineering, and imaging

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: 218, P. 115522 - 115522

Published: Jan. 22, 2025

Language: Английский

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Harnessing the Potential of Exosomes in Therapeutic Interventions for Brain Disorders

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2491 - 2491

Published: March 11, 2025

Exosomes, which are nano-sized natural vesicles secreted by cells, crucial for intercellular communication and interactions, playing a significant role in various physiological pathological processes. Their characteristics, such as low toxicity immunogenicity, high biocompatibility, remarkable drug delivery capabilities—particularly their capacity to traverse the blood–brain barrier—make exosomes highly promising vehicles administration treatment of brain disorders. This review provides comprehensive overview exosome biogenesis isolation techniques, strategies loading functionalization exosomes, exosome-mediated barrier penetration mechanisms, with particular emphasis on recent advances exosome-based Finally, we address opportunities challenges associated utilizing system brain, summarizing barriers clinical translation proposing future research directions.

Language: Английский

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DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 31, 2024

Lysosomes help maintain cellular proteostasis, and defects in lysosomal positioning function can cause disease, including neurodegenerative disorders. The spatiotemporal distribution of lysosomes is regulated by small GTPases Rabs, which are activated guanine nucleotide exchange factors (GEFs). DENN domain proteins the largest family Rab GEFs. Using a cell-based assay, we screened DENND6A, member protein against all known Rabs identified it as potential GEF for 20 Rab34. Here, demonstrate that DENND6A activates Rab34, recruits RILP/dynein complex to lysosomes, promoting lysosome retrograde transport. Further, identify an effector Arl8b, major regulatory GTPase on lysosomes. We Arl8b peripheral activate Rab34 initiate transport, regulating nutrient-dependent juxtanuclear repositioning. Loss impairs autophagic flux. Our findings support model whereby Arl8b/DENND6A/Rab34-dependent trafficking controls autophagy.

Language: Английский

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Autophagy orchestrates the crosstalk between cells and organs

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(9)

Published: July 19, 2023

Abstract Over the recent years, it has become apparent that a deeper understanding of cell‐to‐cell and organ‐to‐organ communication is necessary to fully comprehend both homeostatic pathological states. Autophagy indispensable for cellular development, function, homeostasis. A crucial aspect autophagy can also mediate these processes through its secretory role. The autophagy‐derived secretome relays extracellular signals in form nutrients, proteins, mitochondria, vesicles. These crosstalk mediators functionally shape cell fate decisions, tissue microenvironment systemic physiology. diversity secreted cargo elicits an equally diverse type responses, which span over metabolic, inflammatory, structural adaptations disease We review here emerging role between different types organs discuss mechanisms involved.

Language: Английский

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Developing anti-TDE vaccine for sensitizing cancer cells to treatment and metastasis control

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 27, 2025

Tumor-derived exosomes (TDEs) mediate oncogenic communication, which modifies target cells to reinforce a tumor-promoting microenvironment. TDEs support cancer progression by suppressing anti-tumor immune responses, promoting metastasis, and conferring drug resistance. Thus, targeting could improve the efficacy of anti-cancer treatments control metastasis. Current strategies inhibit TDE-mediated communication including drug-based genetic modification-based inhibition TDE release and/or uptake, have proved be inefficient. In this work, we propose surface engineering express foreign antigens that will trigger life-long anti-TDE responses. The possibility combining vaccines with other such as chemotherapy, radiotherapy, targeted therapy, surgery is also explored.

Language: Английский

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Mechanisms of Asymmetrical Exosome Release from Polarized Epithelial Cells: Implications for the Molecular Basis of Exosomal Heterogeneity

Published: Jan. 1, 2025

Abstract Exosomes are small extracellular vesicles of endocytic origin and secreted into the space by fusion between intraluminal vesicle (ILV)-containing multivesicular bodies (MVBs) plasma membrane. It has recently been shown that a single cell such as an epithelial secretes distinct types exosomes having different protein compositions (referred to “exosomal heterogeneity”). Polarized cells have two membrane domains (an apical basolateral membrane), which separated tight junctions. Two exosome subtypes, i.e., exosomes, asymmetrically from side side, respectively, cell. These subtypes independently regulated mechanisms in terms ILV (exosome precursor) biogenesis MVB transport On formation is ALIX–syntenin-1–syndecan-1 complex formed transported GTPases Rab27 Rab37. neutral sphingomyelinase 2 (nSMase2)-mediated ceramide production machinery, Rab39–UACA–BORC. also retained nonpolarized likely contribute genesis exosomal heterogeneity cells.

Language: Английский

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Bro1 proteins determine tumor immune evasion and metastasis by controlling secretion or degradation of multivesicular bodies

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

Published: April 1, 2025

Language: Английский

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