Reserve Autophagic Capacity in Alveolar Epithelia Provides a Replicative Niche for Influenza A Virus

Hahn, David; Na, Cheng-Lun; Weaver, Timothy E.

doi:10.1165/rcmb.2013-0437oc

Cited by 24 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following inflation fixation, lung slices were incubated with 2% lanthanum nitrate in fixative at room temperature overnight, followed by routine preparation for TEM4546. Electron micrographs were collected using a Hitachi H-7650 TEM (Hitachi High Technologies America, Inc., Dallas, TX) equipped with an AMT transmission electron microscope charge-coupled device camera (Advanced Microscopy Techniques, Woburn, MA).…”

Section: Methodsmentioning

confidence: 99%

The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis

Yang

Luo

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Mitochondria synthesize select phospholipids but lack the machinery for synthesis of the most abundant mitochondrial phospholipid, phosphatidylcholine (PC). Although the phospholipid transfer protein Stard7 promotes uptake of PC by mitochondria, the importance of this pathway for mitochondrial and cellular homeostasis represents a significant knowledge gap. Haploinsufficiency for Stard7 is associated with significant exacerbation of allergic airway disease in mice, including an increase in epithelial barrier permeability. To test the hypothesis that Stard7 deficiency leads to altered barrier structure/function downstream of mitochondrial dysfunction, Stard7 expression was knocked down in a bronchiolar epithelial cell line (BEAS-2B) and specifically deleted in lung epithelial cells of mice (Stard7epi∆/∆). Stard7 deficiency was associated with altered mitochondrial size and membrane organization both in vitro and in vivo. Altered mitochondrial structure was accompanied by disruption of mitochondrial homeostasis, including decreased aerobic respiration, increased oxidant stress, and mitochondrial DNA damage that, in turn, was linked to altered barrier integrity and function. Both mitochondrial and barrier defects were largely corrected by targeting Stard7 to mitochondria or treating epithelial cells with a mitochondrial-targeted antioxidant. These studies suggest that Stard7-mediated transfer of PC is crucial for mitochondrial homeostasis and that mitochondrial dysfunction contributes to altered barrier permeability in Stard7-deficient mice.

show abstract

Section: Methodsmentioning

confidence: 99%

The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis

Yang

Luo

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The same study showed that PINK1−/− (but not Parkin−/−) mice are protected against cigarette smoke-induced mitochondrial dysfunction 44. The deleterious role of mitophagy in COPD is challenged by recent findings in which autophagy-defective Atg5−/− aged mice displayed defective mitochondria in bronchial epithelial cells that were associated with altered lung mechanics 49. Additional evidence suggests that defective mitophagy might be detrimental as in macrophages from smokers mitophagy is impaired due to a failure in the autophagic flux (figure 3).…”

Section: Defective Mitochondrial Function In Copdmentioning

confidence: 99%

Accelerated ageing of the lung in COPD: new concepts

Mercado

Ito

Barnes³

2015

Thorax

277

206

View full text Add to dashboard Cite

The rise in life expectancy worldwide has been accompanied by an increased incidence of age-related diseases, representing an enormous burden on healthcare services and society. All vital organs lose function with age, and this is well described in the lung, with a progressive decline in pulmonary function after the age of about 25 years. The lung ages, like any other organ, with progressive functional impairment and reduced capacity to respond to environmental stresses and injury. Normal physiological ageing results in enlarged alveolar spaces and loss of lung elasticity in the elderly known as 'senile emphysema', whereas in COPD there is destruction of the alveolar walls and fibrosis of peripheral airways. However, COPD shows striking age-associated features, such as an increase in cellular senescence, stem cell exhaustion, increased oxidative stress, alteration in the extracellular matrix and a reduction in endogenous antiageing molecules and protective pathways such as autophagy. In this review we discuss the evidence showing how oxidative stress induces accelerated ageing by upregulating the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT/mechanistic target of rapamycin signalling pathway resulting in depletion of stem cells, defective autophagy, reduced antioxidant responses and defective mitochondrial function thus generating further oxidative stress. Understanding the mechanisms of accelerated ageing in COPD may identify novel therapeutic approaches.

show abstract

“…Interestingly, the production of specific influenza virus proteins (hemagglutinin and M2) stimulates autophagy [211], and the virus requires the autophagy pathway for optimal replication [212,213]. However, M2 concurrently limits autophagosome fusion with lysosomes [214,215].…”

Section: Pathogens Differentially Interfere With the Inflammasomes Anmentioning

confidence: 99%

Checks and Balances between Autophagy and Inflammasomes during Infection

Seveau

Turner

Gavrilin

et al. 2018

Journal of Molecular Biology

View full text Add to dashboard Cite

Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer's disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however, less is known about the interplay between autophagy and inflammasome assembly, although it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.

show abstract

Reserve Autophagic Capacity in Alveolar Epithelia Provides a Replicative Niche for Influenza A Virus

Cited by 24 publications

References 43 publications

The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis

The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and Epithelial Cell Homeostasis

Accelerated ageing of the lung in COPD: new concepts

Checks and Balances between Autophagy and Inflammasomes during Infection

Contact Info

Product

Resources

About