The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense

Franco, Luis H.; Nair, Vidhya R.; Scharn, Caitlyn R.; Xavier, Ramnik J.; Torrealba, José; Shiloh, Michael U.; Levine, Beth

doi:10.1016/j.chom.2016.11.002

Cited by 190 publications

(163 citation statements)

References 42 publications

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“…Dopamine through the dopamine D1 receptor (D1DR) leads to the production of cAMP, which in turn binds NLRP3 promoting MARCH7-mediated K48 ubiquitination and its degradation by autophagy [32]. Although classically K63-polyubiquitin chains mediate autophagy degradation, K48 chains can also lead to degradation by this pathway [33]. Whether this pathway was also involved in PARKIN-mediated NLRP3 regulation has not been investigated.…”

Section: Role Of E1-e2-e3 Enzymes In Canonical Nlrp3 Inflammasome Actmentioning

confidence: 99%

Control of the inflammasome by the ubiquitin system

López-Castejón

2019

The FEBS Journal

111

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Inflammation is the body’s response to danger. One of the first immune cell types to encounter danger is the macrophage. Macrophages sense danger signals such as extracellular ATP or bacterial toxins, derived from tissue damage or infection, and initiate the activation of an intracellular molecular complex called the inflammasome. The inflammasome consists of a cytosolic pattern recognition receptor, an adaptor molecule ASC (apoptosis‐associated speck‐like protein containing a CARD) and the protease caspase‐1. Assembly of the complex leads to the cleavage and activation of caspase‐1 that triggers processing and release of the cytokines interleukin (IL)‐1β and IL‐18, and ultimately cell death via the process of pyroptosis. The ability to sense and respond to danger appropriately is critical for maintaining immune homeostasis. Dysregulation of inflammasomes contributes to the progression of chronic diseases prevalent in the ageing population, such as Alzheimer’s disease, COPD and metabolic disease; hence, it is critical that activation of the inflammatory response and inflammasome activation are tightly regulated. Post‐translational modifications (PTMs) such as ubiquitination have recently emerged as important regulators of inflammasome assembly. However, the mechanisms by which PTMs regulate the inflammasome are still not understood. This review aims to summarize our knowledge to date on how the ubiquitin system controls inflammasome activation and where this area of research is heading.

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Section: Role Of E1-e2-e3 Enzymes In Canonical Nlrp3 Inflammasome Actmentioning

confidence: 99%

Control of the inflammasome by the ubiquitin system

López-Castejón

2019

The FEBS Journal

111

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“…While this suggests a role in Pink1/ Parkin mitophagy this has not been studied further. More recently, SMURF1 was rather linked to selective autophagy of intracellular bacteria, termed xenophagy (Franco et al, 2017).…”

Section: Ambra1 and Smurf1mentioning

confidence: 99%

How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways

Zimmermann

Reichert

2017

Biological Chemistry

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Mitochondria are indispensable cellular organelles providing ATP and numerous other essential metabolites to ensure cell survival. Reactive oxygen species (ROS), which are formed as side reactions during oxidative phosphorylation or by external agents, induce molecular damage in mitochondrial proteins, lipids/ membranes and DNA. To cope with this and other sorts of organellar stress, a multi-level quality control system exists to maintain cellular homeostasis. One critical level of mitochondrial quality control is the removal of damaged mitochondria by mitophagy. This process utilizes parts of the general autophagy machinery, e.g. for the formation of autophagosomes but also employs mitophagy-specific factors. Depending on the proteins utilized mitophagy is divided into receptor-mediated and ubiquitin-mediated mitophagy. So far, at least seven receptor proteins are known to be required for mitophagy under different experimental conditions. In contrast to receptor-mediated pathways, the Pink-Parkin-dependent pathway is currently the best characterized ubiquitin-mediated pathway. Recently two additional ubiquitin-mediated pathways with distinctive similarities and differences were unraveled. We will summarize the current state of knowledge about these multiple pathways, explain their mechanism, and describe the regulation and crosstalk between these pathways. Finally, we will review recent evidence for the evolutionary conservation of ubiquitin-mediated mitophagy pathways.

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“…These autophagy adaptors, which include NBR1, NDP52, optineurin, p62 and TAX1BP1, are important for the antibacterial response and may have functions extending beyond phagophore recruitment (Verlhac et al, 2015, Randow and Youle, 2014, Tumbarello et al, 2015). Less is known about how microorganisms are targeted by Ub chains, although E3 Ub ligases targeting cytosolic S. typhimurium (Huett et al, 2012, Noad et al, 2017, van Wijk et al, 2017) and M. tuberculosis -containing vacuoles (Manzanillo et al, 2013, Franco et al, 2017) have been identified. Interestingly, the recognition of extracellular bacterial DNA by the cGAS-STING pathway, originally identified as activating the type I interferon response, seems to be a trigger for the ubiquitylation of M. tuberculosis -containing vacuoles during infection (Watson et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation

Mitchell

Isberg

2017

Cell Host & Microbe

101

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Summary Recent excitement regarding immune clearance of intracellular microorganisms has focused on two systems that maintain cellular homeostasis. One system includes cellular autophagy components that mediate degradation of pathogens in membrane-bound compartments, in a process termed xenophagy. The second system is driven by interferon– regulated GTPases that promote rupture of pathogen-containing vacuoles and microbial degradation. In the case of xenophagy, pathogen sequestration and compartmentalization suppress inflammation. In contrast, interferon-driven events can lead to exposure of pathogen-associated molecular patterns to the host cytosol with consequent inflammasome activation. Paradoxically, signals and factors involved in xenophagy also mobilize interferon-regulated GTPases, which drive the inflammatory response, indicating considerable crosstalk between these pathways. How these responses are prioritized remains to be understood. In this review, we describe mechanisms of intracellular pathogen clearance that rely on the autophagy machinery and interferon-regulated GTPases, and speculate how these pathways engage each other to balance pathogen elimination with inflammation.

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The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense

Cited by 190 publications

References 42 publications

Control of the inflammasome by the ubiquitin system

Control of the inflammasome by the ubiquitin system

How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways

Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation

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