Ubiquitin and Ubiquitin‐Like Modifications in Organelle Stress Signaling: Ub, Ub, Ub, Ub, Stayin’ Alive, Stayin’ Alive DOI Creative Commons
Élodie Lafont, Éric Chevet

BioEssays, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

ABSTRACT Due to various intracellular and external cues, cellular organelles are frequently stressed in both physiological pathological conditions. Sensing these stresses initiates signaling pathways which may lead adaptation of the cells or trigger its their death. At unicellular level, this stress involves a crosstalk between different organelles. multicellular such can contribute indicate presence cell neighboring cells. Here, we highlight crucial diverse roles played by Ubiquitin Ubiquitin‐like modification organelle signaling.

Language: Английский

NEMO Family of Proteins as Polyubiquitin Receptors: Illustrating Non-Degradative Polyubiquitination’s Roles in Health and Disease DOI Creative Commons
Chuan-Jin Wu

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 304 - 304

Published: Feb. 18, 2025

The IκB kinase (IKK) complex plays a central role in many signaling pathways that activate NF-κB, which turns on battery of genes important for immune response, inflammation, and cancer development. Ubiquitination is one the most prevalent post-translational modifications proteins best known targeting substrates proteasomal degradation. investigations NF-κB pathway primed unveiling non-degradative roles protein ubiquitination. NF-κB-essential modulator (NEMO) IKK regulatory subunit essential activation by diverse intrinsic extrinsic stimuli. studies centered NEMO as polyubiquitin-binding have remarkably advanced understandings how transmits signals to laid foundation determining molecular events demonstrating ubiquitination major driving element activation. Furthermore, these largely solved enigma can be activated employ distinct sets intermediaries transmitting signals. NEMO-related include optineurin, ABIN1, ABIN2, ABIN3, CEP55, ubiquitin chain receptors, play key sensing embodied different topologies polyubiquitin chains variety cellular processes body responses. Studies multifaceted promoted understanding about functions intracellular signaling, trafficking, proteostasis, DNA damage cell cycle control. In this review, I will also discuss dysfunction family protein-mediated associated with various diseases, including disorders, neurodegenerative cancer, microbial virulence factors target induce pathogenesis or manipulate host response. A profound bases valuable developing tailored approaches therapeutic purposes.

Language: Английский

Citations

0
Mitochondrial sites of contact with the nucleus DOI
Michelangelo Campanella, Brindha Kannan

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(6)

Published: April 26, 2024

Membrane contact sites (MCS) between mitochondria and the nucleus have been recently described. Termed associated (NAM), they prime expression of genes required for cellular resistance to stressors, thus offering a tethering mechanism homeostatic communication. Here, we discuss composition NAM their physiological pathological significance.

Language: Английский

Citations

3
Regulation of Mitochondria-Derived Immune Activation by ‘Antiviral’ TRIM Proteins DOI Creative Commons
Seeun Oh, Michael A. Mandell

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1161 - 1161

Published: July 19, 2024

Mitochondria are key orchestrators of antiviral responses that serve as platforms for the assembly and activation innate immune-signaling complexes. In response to viral infection, mitochondria can be triggered release immune-stimulatory molecules boost interferon production. These same released by damaged induce pathogenic, antiviral-like immune in absence infection. This review explores how members tripartite motif-containing (TRIM) protein family, which recognized their roles defense, regulate mitochondria-based activation. TRIMs essential components signal transduction pathways function directly acting restriction factors. carry out conceptually similar activities when controlling related mitochondria. First, they modulate activated mitochondrial molecules. Second, co-ordinate direct removal associated immune-activating factors through mitophagy. insights broaden scope TRIM actions immunity may implicate diseases with mitochondria-derived inflammation.

Language: Английский

Citations

2
Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity DOI Creative Commons

Martin A. Michel,

Simon R. Scutts, David Komander

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114545 - 114545

Published: July 23, 2024

Language: Английский

Citations

2
In an experimental myocardial infarction model, L-arginine pre-intervention may exert cardioprotective effects by regulating OTULIN levels and mitochondrial dynamics DOI Creative Commons
Sercan Kaya, Tuba Yalçın

Cell Stress and Chaperones, Journal Year: 2023, Volume and Issue: 28(6), P. 811 - 820

Published: Aug. 29, 2023

The experimental myocardial infarction (MI) model originating from isoproterenol (ISO) is frequently preferred in research due to its similarity MI-induced damage humans. Beneficial effects of L-arginine (L-Arg), a semi-essential amino acid, cardiovascular diseases have been shown many studies. This study was carried out determine whether L-Arg pre-intervention has protective on heart tissue the MI model. 28 rats used were randomly divided into 4 equal groups: control, L-Arg, ISO, and L-Arg+ISO. Upon completion all applications, cardiac markers serum biochemical, histopathological, immunohistochemical examinations tissues performed. Cardiac markers, histopathological changes, oxidative stress, inflammation, apoptosis increased In addition, administration ISO deregulated OTULIN levels mitochondrial dynamics tissue. However, showed significant effect against changes ISO-induced MI. supplementation with cardioprotective may reduce risks possible pathophysiological processes

Language: Английский

Citations

6
Possible correlated signaling pathways with chronic urate nephropathy: A review DOI Creative Commons

Kaiqing Li,

Yanchun Ma,

Xue Xia

et al.

Medicine, Journal Year: 2023, Volume and Issue: 102(32), P. e34540 - e34540

Published: Aug. 11, 2023

Hyperuricemia nephropathy, also known as gouty refers to renal damage induced by hyperuricemia caused excessive production of serum uric acid or low excretion acid. the persistence symptoms will lead changes in tubular phenotype and accelerate progress fibrosis. The existence progressive aggravation bring a heavy burden patients, their families society, affect quality life reduce well-being. With increase reports on importance related signal pathways pathogenesis nephropathy is becoming more obvious, but most studies are limited upper lower mediating relationship between 1 2 pathways. research comprehensiveness breadth crosstalk limited. By synthesizing results recent years, this paper explore specific mechanism provide new ideas methods for treatment based variety pathway personal prospects.

Language: Английский

Citations

4
Therapeutic potential of the linalool against cadmium-induced testicular tissue damage DOI
Tuba Yalçın, Sercan Kaya

Journal of Trace Elements in Medicine and Biology, Journal Year: 2024, Volume and Issue: 84, P. 127455 - 127455

Published: April 15, 2024

Language: Английский

Citations

1
Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery DOI Creative Commons

Jack Li,

Sijin Liu, Shitao Li

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 28, 2023

Abstract Linear ubiquitination is a distinct type of that involves attaching head-to-tail polyubiquitin chain to substrate protein. Early studies found linear ubiquitin chains are essential for the TNFα- and IL-1-mediated NF-κB signaling pathways. However, recent have discovered at least sixteen substrates, which exhibit broader activity than expected mediate many other pathways beyond signaling. Dysregulation in these has been linked types cancers, such as lymphoma, liver cancer, breast cancer. Since discovery ubiquitin, extensive effort made delineate molecular mechanisms how dysregulation causes tumorigenesis cancer development. In this review, we highlight newly ubiquitination-mediated pathways, advances role different development inhibitors.

Language: Английский

Citations

3
Mitochondrial outer membrane integrity regulates a ubiquitin-dependent NF-κB inflammatory response DOI Creative Commons
Esmee Vringer, Joel S. Riley, A. R. S. Black

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 21, 2023

Abstract Mitochondria are often essential for apoptosis through mitochondrial outer membrane permeabilization (MOMP). This central event enables cytochrome c release leading to caspase activation and rapid cell death. Recently, MOMP has been shown be inherently pro-inflammatory, instance, by enabling DNA-dependent of cGAS-STING signalling. Alongside having emerging functions in health disease, associated inflammation can also elicit anti-tumour immunity. Nonetheless, how triggers the counteracts this remains poorly defined. We find that upon MOMP, mitochondria ubiquitylated a promiscuous manner targeting proteins localised both inner membranes. Mitochondrial ubiquitylation serves recruit adaptor molecule, NEMO, pro-inflammatory NF-κB disruption integrity different means leads engagement similar signalling platform. Thus, directly controls inflammation, such permeabilised initiate may important various pathophysiological MOMP-associated inflammation.

Language: Английский

Citations

2
Linear ubiquitination at damaged lysosomes induces local NF-κB activation and controls cell survival DOI Open Access
Laura Zein,

Marvin Dietrich,

Denise Balta

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 6, 2023

Abstract Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of material. Maintenance lysosomal integrity is essential homeostasis membrane permeabilization (LMP), induced by lysosomotrophic agents, sensitizes towards cell death. Damaged lysosomes repaired or degraded via lysophagy, during which glycans, exposed on ruptured membranes, recognized galectins leading to K48- K63-linked poly-ubiquitination (poly-Ub) proteins followed recruitment autophagic machinery degradation. Linear (M1) poly-Ub, catalyzed E3 ligase linear ubiquitin chain assembly complex (LUBAC) removed OTU domain-containing deubiquitinase with linkage specificity (OTULIN) exerts important functions in immune signaling survival, but role M1 poly-Ub remains largely unexplored. Here, we demonstrate that damaged decorated a LUBAC-, OTULIN- K63-dependent manner. LMP-induced at contributes lysosome degradation, recruits nuclear factor κ-B (NF-κB) modulator (NEMO) locally activates inhibitor NF-ĸB kinase (IKK) trigger NF-κB activation K63 poly-Ub-dependent Inhibition enhances LMP- OTULIN-dependent death, indicating pro-survival LMP potentially lysophagy. Finally, occurs L-leucyl-leucine methyl ester (LLOMe)-damaged primary mouse neurons pluripotent stem (iPSC)-derived human dopaminergic neurons. Together, our results reveal novel homeostasis, lysosomes, implications signaling, inflammation

Language: Английский

Citations

2