SLMO is Required for Maintaining Mitochondrial Morphology by Mediating Intramitochondrial Transport of Phosphatidylserine DOI
Siwen Zhao, Xuguang Jiang, Ning Li

et al.

Published: Jan. 1, 2023

Phospholipids are critical building blocks of mitochondria, and mitochondrial proper functions architecture rely on its phospholipids majorly transported from the endoplasmic reticulum (ER). Here, we show that among major phospholipids, trafficking phosphatidylserine (PS) ER to mitochondria converting PS phosphatidylethanolamine (PE) in inner membrane (IMM) for maintaining morphology function. Using a forward genetic screen Drosophila, found Slowmo (SLMO) specifically transfer outer (OMM) IMM within boundary (IBM) domain, is required shaping morphology. In slmo mutants, flux disrupted, leading fragmentation, loss cristae, reduced function, locomotion phenotypes, neurodegeneration. Importantly, role SLMO plays conserved humans via SLMO2 protein independent dynamics. Our results highlight importance PSS-SLMO-PISD pathway structure function mitochondria.

Language: Английский

Canonical and non-canonical roles of complement in atherosclerosis DOI
Pasquale Maffia, Claudio Mauro, Ayden Case

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(11), P. 743 - 761

Published: April 10, 2024

Language: Английский

Citations

13
Obesity and risk of diseases associated with hallmarks of cellular ageing: a multicohort study DOI Creative Commons
Mika Kivimäki, Philipp Frank,

Jaana Pentti

et al.

The Lancet Healthy Longevity, Journal Year: 2024, Volume and Issue: 5(7), P. e454 - e463

Published: June 27, 2024

BackgroundAgeing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology many age-related diseases. We examined whether obesity is associated with an increased risk developing such hallmark-related diseases.MethodsIn this multicohort study, we included people aged 38–72 years data on weight, height, and waist circumference measured during clinical examination at baseline between March 13, 2006, Oct 1, 2010, from UK Biobank follow-up until Nov 12, 2021. To test reproducibility findings (replication analysis), used 40 or older Finnish Public Sector study Health Social Support who responded to surveys, had BMI, were successfully linked electronic health records national registers up Dec 31, 2016. Obesity characteristics assessed baseline. Via linkage records, participants followed for 83 diseases related nine ageing hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, senescence, stem cell exhaustion, altered intercellular communication). Outcomes first instance disease, addition co-occurrence three more mortality.Findings496 530 adults (mean age 57·0 [SD 8·1]) primary analysis, 249 48·2 [6·4]) cohorts replication analysis. Median was 12·7 (IQR 12·0–13·4) 14·0 (8·0–15·0) cohorts. After adjusting demographic characteristics, lifestyle factors, depression, (BMI ≥30·0 kg/m2) 1·40 (95% CI 1·38–1·41) times higher hazard ratio disease than those healthy weight 18·5–24·9 kg/m2). The corresponding ratios co-occurring 2·92 2·64–3·22) 2·73 (2·46–3·02) 2·33 (2·10–2·60) 2·30 (2·14–2·48) 2·23 (2·04–2·45) 2·02 (1·89–2·16) communication, 2·01 (1·89–2·15) 1·83 (1·67–2·00) 1·39 (1·27–1·52) genomic instability. These replicated In both studies, associations other factors (low education, unhealthy dietary [available only Biobank], smoking, high alcohol consumption, physical inactivity, depression) weaker obesity. 45–60% excess mortality attributable diseases.InterpretationObesity might important development ageing. Tackling mechanisms could potentially help reduce burden resulting epidemic.FundingWellcome Trust, Medical Research Council, US National Institute Aging, Academy Finland, Foundation Cardiovascular Research.TranslationsFor German translations abstract see Supplementary Materials section.

Language: Английский

Citations

9
Inflammasome and pyroptosis in autoimmune liver diseases DOI Creative Commons
Jixuan Wang,

Zhiwen Sun,

Jingri Xie

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 8, 2023

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), sclerosing (PSC), and IgG4-related (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which all defined by an aberrant immune system attack on liver. Most previous studies have shown that apoptosis necrosis two major modes hepatocyte death in AILDs. Recent reported inflammasome-mediated pyroptosis is critical for inflammatory response severity injury This review summarizes our present understanding inflammasome activation function, as well connections among inflammasomes, pyroptosis, AILDs, thus highlighting shared features across disease models gaps knowledge. In addition, we summarize correlation NLRP3 liver-gut axis, injury, intestinal barrier disruption PBC PSC. We differences microbial metabolic characteristics between PSC IgG4-SC, highlight uniqueness IgG4-SC. explore different roles acute chronic cholestatic complex controversial crosstalk various types cell also discuss most up-to-date developments inflammasome- pyroptosis-targeted medicines disorders.

Language: Английский

Citations

16
Complement, complosome, and complotype: A perspective DOI Open Access
Parul Singh, Claudia Kemper

European Journal of Immunology, Journal Year: 2023, Volume and Issue: 53(12)

Published: April 30, 2023

Recent rapid progress in key technological advances, including the broader accessibility of single-cell "omic" approaches, have allowed immunologists to gain important novel insights into contributions individual immune cells protective immunity and immunopathologies. These also taught us that there is still much uncover about (cellular) networks underlying responses. For example, last decade, studies on a component innate immunity, complement system, defined intracellularly active (the complosome) as orchestrator normal cell physiology. This added an unexpected facet biology complement, which was long considered fully explored. Here, we will summarize succinctly known activation modes functions complosome provide perspective origins intracellular complement. We make case for extending assessments complotype, inherited landscape common variants genes, complosome, reassessing patients with serum deficiencies perturbations. Finally, discuss where see current opportunities hurdles dissecting compartmentalization activities toward better understanding their cellular function health disease.

Language: Английский

Citations

16
Role of pattern recognition receptors in the development of MASLD and potential therapeutic applications DOI Open Access
Lili Yu, Feifei Gao, Yaoxin Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116724 - 116724

Published: May 17, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent diseases worldwide, and its occurrence is strongly associated with obesity, insulin resistance (IR), genetics, metabolic stress. Ranging from simple fatty to steatohepatitis (MASH), even severe complications such as fibrosis advanced cirrhosis or hepatocellular carcinoma, underlying mechanisms MASLD progression are complex involve multiple cellular mediators related signaling pathways. Pattern recognition receptors (PRRs) innate immune system, including Toll-like (TLRs), C-type lectin (CLRs), NOD-like (NLRs), RIG-like (RLRs), DNA receptors, have been demonstrated potentially contribute pathogenesis for MASLD. Their pathways can induce inflammation, mediate oxidative stress, affect gut microbiota balance, ultimately resulting in hepatic steatosis, inflammatory injury fibrosis. Here we review available literature regarding involvement PRR-associated signals pathogenic clinical features MASLD, vitro animal models We also discuss emerging targets PRRs drug developments that involved agent therapies intended arrest reverse progression, thus enabling refinement therapeutic accelerate development.

Language: Английский

Citations

6
Targeting NAD+ Metabolism to Modulate Autoimmunity and Inflammation DOI
Jing Wu, Kim Han, Michael N. Sack

et al.

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 212(7), P. 1043 - 1050

Published: March 18, 2024

Abstract NAD+ biology is involved in controlling redox balance, functioning as a coenzyme numerous enzymatic reactions, and cofactor for Sirtuin enzymes substrate multiple regulatory enzyme reactions within outside the cell. At same time, levels are diminished with aging consumed during development of inflammatory autoimmune diseases linked to aberrant immune activation. Direct augmentation via salvage Priess-Handler pathways being investigated putative therapeutic intervention improve healthspan inflammation-linked diseases. In this review, we survey its pivotal roles regulation immunity inflammation. Furthermore, discuss emerging studies evaluate boosting murine models human diseases, highlight areas research that remain unresolved understanding mechanisms action these nutritional supplementation strategies.

Language: Английский

Citations

5
Unveiling the orchestration of T-cell dynamics: A comprehensive examination of their crucial role in revolutionizing immunotherapy for pancreatic and colon cancers DOI

Sridevi Mardham,

Soumya Dakshinamurthy

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 199 - 232

Published: Jan. 1, 2025

Language: Английский

Citations

0
Research Progress of Non-Alcoholic Fatty Liver Disease from the Perspective of Intestinal Flora DOI

雪 罗

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(03), P. 477 - 490

Published: Jan. 1, 2025

Language: Английский

Citations

0
Liver-specific actions of GH and IGF1 that protect against MASLD DOI
Rhonda D. Kineman,

Mercedes Del Rio-Moreno,

David J. Waxman

et al.

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

Language: Английский

Citations

2
BLOC1S1 control of vacuolar organelle fidelity modulates TH2 cell immunity and allergy susceptibility. DOI Open Access
Rahul Sharma, Kaiyuan Wu, Kim Han

et al.

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

Published: March 27, 2024

ABSTRACT The levels of biogenesis lysosome organelles complex 1 subunit (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis function. Reduced fidelity these vacuolar is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role BLOC1S1 CD4 + T cells, may further advance our understanding regulatory events linked to and/or endolysosomal function adaptive immunity. Transcript canonical transcription factors driving polarization response activation showed that, H 2 regulator GATA3 phosphorylated STAT6 were preferentially induced depleted primary (TKO) cells. In parallel, both receptor IL-4, IL-5 IL-13 markedly absence BLOC1S1. At level, DNA leakage evoked cGAS-STING NF-kB pathway with subsequent polarization. induction autophagy rapamycin reduced cytosolic mtDNA reverses signatures. Furthermore, genetic knockdown STING NF-κB inhibition ameliorated this cascade TKO Finally, at a functional mice displayed increased susceptible allergic conditions including atopic dermatitis asthma. conclusion, depletion mediated disruption integrity initiate predominant responsive phenotype via STING-NF-κB driven signaling program.

Language: Английский

Citations

1