The role of autophagy in bacterial infections

Castrejón-Jiménez, Nayeli Shantal; Leyva-Paredes, Kahiry; Hernández-González, Juan Carlos; Luna-Herrera, Julieta; Garcı́a-Pérez, Blanca Estela

doi:10.5582/bst.2015.01035

Cited by 51 publications

(39 citation statements)

References 111 publications

(121 reference statements)

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“…In some cases, as discussed below in the case of mitophagy, this overlap is cooperative to mediate delivery to autophagosomes[60,61]. In other cases, such as xenophagy, multiple different autophagy receptors appear capable of mediating the process individually[62]. This suggests that there is another layer of complexity and regulation with regards to recognition of cargo or activation of specific selective autophagy receptors in response to selective autophagy stimuli.…”

Section: Selective Autophagy Receptors: Ubiquitin-mediated Cargo Recomentioning

confidence: 99%

“…p62 is also involved in the selective autophagy of ubiquitylated cytosolic bacteria in a process called xenophagy (selective autophagy of pathogens including bacteria and viruses)[18,62]. Indeed, autophagy had been implicated in the degradation of cytosolic bacteria as part of the innate immune system for several decades but the molecular details for targeting have only recently become clear.…”

Section: P62: Multi-functional Selective Autophagy Receptor With Rolementioning

confidence: 99%

“…While it is clear that each of the studied selective autophagy receptors contribute to xenophagy, further work is required to clarify the relative contributions of each. Much work has been performed examining the role of autophagy and selective autophagy and how it is integrated with the host immune response in a wide variety of bacterial and viral infections and is reviewed elsewhere[18,62,100,101]. Understanding the role of selective autophagy here may prove relevant for future therapeutic intervention.…”

Section: P62: Multi-functional Selective Autophagy Receptor With Rolementioning

confidence: 99%

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Mechanisms of Selective Autophagy in Normal Physiology and Cancer

Mancias

Kimmelman

2016

Journal of Molecular Biology

150

118

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Selective autophagy is critical for regulating cellular homeostasis by mediating lysosomal turnover of a wide variety of substrates including proteins, aggregates, organelles, and pathogens via a growing class of molecules termed selective autophagy receptors. The molecular mechanisms of selective autophagy receptor action and regulation are complex. Selective autophagy receptors link their bound cargo to the autophagosomal membrane by interacting with lipidated ATG8 proteins (LC3/GABARAP) that are intimately associated with the autophagosome membrane. The cargo signals that selective autophagy receptors recognize are diverse but their recognition can be broadly grouped into two classes, ubiquitin-dependent cargo recognition versus ubiquitin-independent. The roles of post-translational modification of selective autophagy receptors in regulating these pathways in response to stimuli are an active area of research. Here we will review recent advances in the identification of selective autophagy receptors and their regulatory mechanisms. Given its importance in maintaining cellular homeostasis, disruption of autophagy can lead to disease including neurodegeneration and cancer. The role of autophagy in cancer is complex as autophagy can mediate promotion or inhibition of tumorigenesis. Here we will also review the importance of autophagy in cancer with a specific focus on the role of selective autophagy receptors.

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Section: Selective Autophagy Receptors: Ubiquitin-mediated Cargo Recomentioning

confidence: 99%

Section: P62: Multi-functional Selective Autophagy Receptor With Rolementioning

confidence: 99%

Section: P62: Multi-functional Selective Autophagy Receptor With Rolementioning

confidence: 99%

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Mechanisms of Selective Autophagy in Normal Physiology and Cancer

Mancias

Kimmelman

2016

Journal of Molecular Biology

150

118

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“…That said, among the 645 DE genes between resistant and susceptible individuals in the non-infected state, there were many interesting genes involved in important innate immune activities critical for fighting MTB and other pathogens such as autophagy 27, 28 , phagolysosomal acidification, and antigen processing. In particular, FEZ2 , a suppressor of autophagosome formation 29 , was down-regulated when DCs were infected with MTB; however, in the non-infected DCs, this gene has elevated expression level in susceptible compared with resistant individuals.…”

Section: Discussionmentioning

confidence: 99%

Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells

Blischak

Tailleux

Myrthil

et al. 2017

Sci Rep

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Tuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world’s population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated reasonable performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.

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“…7 Therefore, autophagy mechanisms play important roles in maintaining cellular homeostasis, organelle biogenesis, adjusting cellular energy, and as a specific protection and defense device in contradiction to microorganisms, a process specifically known as xenophagy. [8][9][10][11] Autophagy is considered an active flux which includes sequential steps initiating from formation of nucleation and isolation of cytoplasmic materials by an isolation membrane (phagophore formation), which later forms a double-membrane structure named autophagosome which finally moves toward and fuses with lysosomes to form autophagolysosomes for the degradation of its content. [12][13][14][15] In the autophagy process, several autophagy genes (Atg) are involved which tightly regulate the autophagy process.…”

mentioning

confidence: 99%