The Critical Role of Autophagy and Phagocytosis in the Aging Brain DOI Open Access
Stephen C. Bondy,

Meixia Wu

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 57 - 57

Published: Dec. 25, 2024

As the organism ages, there is a decline in effective energy supply, and this retards ability to elaborate new proteins. The consequences of are especially marked gradual brain function. senescence cells their constituent organelles ultimately cause aging entire nervous system. What less immediately obvious that also accompanied by failure catabolic events lead removal non-functional ineffective subcellular components. non-working cellular elements within essential order allow appearance fresh with full range capacities. Thus, maintenance operative mechanisms for dispersal failed tissue components important, its diminished capacity significant contributory factor onset progression age-related neurological disorder. This report discusses underlying autophagy phagocytosis how these can be adversely modulated as proceeds. means which recycling may reinstated aged considered.

Language: Английский

Roles of lipid droplets and related proteins in metabolic diseases DOI Creative Commons
Zhongyang Zhang,

Zhenghang Yu,

Dianyuan Liang

et al.

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 19, 2024

Abstract Lipid droplets (LDs), which are active organelles, derive from the monolayer membrane of endoplasmic reticulum and encapsulate neutral lipids internally. LD-associated proteins like RAB, those in PLIN family, CIDE family participate LD formation development, they players various diseases, metabolic processes (i.e., obesity, non-alcoholic fatty liver disease, autophagy). Our synthesis on existing research includes insights LDs to their mechanisms action, provide an overview needed for advancing into diseases lipid metabolism.

Language: Английский

Citations

4
Molelcuar regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy DOI
Bishnu Prasad Behera, Soumya Ranjan Mishra, Srimanta Patra

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Insights on the crosstalk among different cell death mechanisms DOI Creative Commons
Georgette Eskander, Sherihan G. AbdelHamid, Sara A. Wahdan

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 10, 2025

Language: Английский

Citations

0
Sepsis-induced cardiac dysfunction: mitochondria and energy metabolism DOI Creative Commons

Xueting Yu,

Jie Gao, Chunxiang Zhang

et al.

Intensive Care Medicine Experimental, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 18, 2025

Abstract Sepsis is a life-threatening multi-organ dysfunction syndrome caused by dysregulated host response to infection, posing significant global healthcare challenge. Sepsis-induced myocardial (SIMD) common complication of sepsis, significantly increasing mortality due its high energy demands and low compensatory reserves. The substantial mitochondrial damage rather than cell apoptosis in SIMD suggests disrupted cardiac metabolism as crucial pathophysiological mechanism. Therefore, we systematically reviewed the mechanisms underlying SIMD, including alterations substrates, excitation–contraction coupling processes, dysfunction, autophagy biogenesis, summarizing potential therapeutic targets within them.

Language: Английский

Citations

0
SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics DOI Creative Commons
Laura Trachsel-Moncho,

Chiara Veroni,

Benan John Mathai

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(5)

Published: March 7, 2025

We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy OXPHOS machinery components. In control conditions, localizes to early endocytic compartments in PtdIns3P-dependent manner and modulates trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking late structures containing selected mitochondrial proteins, including COX-IV SAMM50, autophagy proteins SQSTM1/p62 LC3B. The turnover was enhanced SNX10-depleted cells, corresponding reduced respiration citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show levels Cox-IV, well elevated ROS ROS-mediated cell death brain, demonstrating vivo relevance SNX10-mediated modulation bioenergetics.

Language: Английский

Citations

0
Interleukins‐27 Aggravates Liver Injury by Impairing the Antimicrobial Response of Macrophages via the Promotion of Mitochondrial Dysfunction in the Context of Sepsis DOI Creative Commons
Yuehua You, Yuyan Li, Lin Ye

et al.

Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background and Aims: Plasma interleukin (IL)-27 is an important mediator of acute hepatic injury (AHI) associated with sepsis. Mitochondria contribute to the proper regulation macrophage phagocytosis. In this study, we investigated effect IL-27 on mitochondrial function antimicrobial response macrophages in sepsis-associated AHI. Methods: Wild-type (WT) receptor WSX-1 deficient (IL-27R-/-) mice underwent cecal ligation puncture (CLP). The severity injury, inflammatory cytokine levels, pyroptosis, bacterial load liver blood were assessed 24 h after CLP. vitro, RAW264.7 cells peritoneal treated lipopolysaccharide (LPS) and/or IL-27. phagocytosis killing functions detected. Mitochondrial mitophagy detected using western blot, glutathione (GSH)/malondialdehyde (MDA) content measurement, fluorescence staining, JC-1 staining vivo vitro. After treatment nicotinamide mononucleotide (NMN, NAD + precursor), a pharmacologic agent that improves function, response, pyroptosis assessed. Results: IL-27R-/- exhibited marked reduction (based cleaved GSDMD Caspases 1 protein levels), systemic inflammation serum IL-6, IL-10, TNF-α levels) compared WT following CLP, lacking IL-27R displayed significantly higher clearance greater local infection control. Subsequent studies demonstrated directly impaired LPS-induced phagocytosis, capacity, macrophages. Finally, enhanced NMN alleviated pathological inflammation. Conclusions: These findings indicated impairs capacity by aggravating dysfunction aggravate AHI during

Language: Английский

Citations

0
Advanced Spray-Dried Inhalable Microparticles/Nanoparticles of an Innovative Mitophagy Activator for Targeted Lung Delivery: Design, Comprehensive Characterization, Human Lung Cell Culture, and In Vitro Aerosol Dispersion Performance DOI Creative Commons
Hasham S. Sofi,

Andrea J. Lora,

Haley M. Donow

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(11), P. 3540 - 3558

Published: Oct. 15, 2024

Urolithin A (UA) has demonstrated the ability to stimulate mitophagy and enhance mitochondrial cellular health in skeletal muscles humans after oral administration. It is hypothesized that targeted delivery of UA as inhaled dry powders lungs will through biogenesis. This study aimed engineer inhalable excipient-free powder inhalers (DPIs) for pulmonary delivery. The particles were designed by particle engineering from dilute organic solutions using state-of-the-art spray drying technology a closed mode. Comprehensive physicochemical characterization advanced microscopy techniques conducted examine phase behavior, molecular properties, which are necessary rational design inhalation aerosols. Molecular fingerprinting was attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy Raman spectroscopy. Chemical imaging mapping confocal (CRM) IR microscopy. spray-dried (SD) successfully produced at different spraying pump feed rates exhibited favorable properties. SD outstanding vitro aerosol dispersion performance with an FDI-approved human DPI device (Neohaler) correlated rate. In

Language: Английский

Citations

2
Mitochondria in skeletal system-related diseases DOI Open Access

Liang Pei,

Zizhen Yao, Liang Dong

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117505 - 117505

Published: Nov. 4, 2024

Language: Английский

Citations

1
SNX10 regulates the clearance of mitochondrial proteins and mitochondrial bioenergetics DOI Open Access
Laura Trachsel-Moncho, Caterina Veroni, Benan John Mathai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 18, 2024

ABSTRACT We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy OXPHOS machinery components. In control conditions, localizes to early endocytic compartments in PtdIns3P-dependent manner and modulates trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking late structures containing selected mitochondrial proteins, including COX- IV SAMM50, autophagy proteins SQSTM1/p62 LC3B. The turnover COX-IV ATP synthase subunit pSu9 was enhanced SNX10-depleted cells, corresponding reduced respiration citrate activity. Importantly, zebrafish larvae lacking Snx10 show levels COX-IV, well elevated ROS ROS-mediated cell death brain, demonstrating vivo relevance SNX10-mediated modulation bioenergetics. eTOC summary Trachsel-Moncho et al. modulator components homeostasis. They that loss enhances degradation, reduces respiration, increases leading vivo.

Language: Английский

Citations

0
Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1 DOI Creative Commons
Duomeng Yang,

Jason G. Cahoon,

Tingting Geng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

ABSTRACT Ubiquitination is a major posttranslational covalent modification that regulates numerous cellular processes including inflammasome signaling. Cells also contain unanchored ubiquitin chains (polyUb) bind protein targets non-covalently, but their physiological functions in immunity have been appreciated only recently. Here, we report regulatory x domain-containing 1 (UBXN1) activates the noncanonical via Lysin (K) 48- or 63-linked polyUb. UBXN1 deficiency impairs activation of caspase-4/11, secretion inflammasome-dependent cytokines and pyroptosis response to intracellular lipopolysaccharide (LPS). UBXN1-deficient mice are protected from LPS- cecal-ligation-and-puncture-induced sepsis, evidenced by reduced mortality systemic inflammation, compared UBXN1-sufficient littermates. Mechanistically, together with K48/63-linked polyUb sensors LPS, promote assembly activation. Depleting recombinant ubiquitin-specific proteinase 5 (USP5) reduces binding caspase-4/11 signaling, while USP5 inhibitors enhance an UBXN1-dependent manner. Thus, this study identifies critical mechanism involved as potential therapeutic target for sepsis advances fundamental understanding biology.

Language: Английский

Citations

0