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      Mitochondrial dysfunction in lung ageing and disease

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          Abstract

          Mitochondrial biology has seen a surge in popularity in the past 5 years, with the emergence of numerous new avenues of exciting mitochondria-related research including immunometabolism, mitochondrial transplantation and mitochondria-microbe biology. Since the early 1960s mitochondrial dysfunction has been observed in cells of the lung in individuals and in experimental models of chronic and acute respiratory diseases. However, it is only in the past decade with the emergence of more sophisticated tools and methodologies that we are beginning to understand how this enigmatic organelle regulates cellular homeostasis and contributes to disease processes in the lung. In this review, we highlight the diverse role of mitochondria in individual lung cell populations and what happens when these essential organelles become dysfunctional with ageing and in acute and chronic lung disease. Although much remains to be uncovered, we also discuss potential targeted therapeutics for mitochondrial dysfunction in the ageing and diseased lung.

          Abstract

          We provide an up-to-date synopsis of the diverse nature of the mitochondrion in maintaining cellular homeostasis in an array of lung cell types and what happens when these pathways become dysfunctional with ageing and with acute or chronic lung disease. https://bit.ly/30jNKjZ

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          Most cited references200

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          A role for mitochondria in NLRP3 inflammasome activation.

          An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
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            Estimates of global seasonal influenza-associated respiratory mortality: a modelling study

            Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015.
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              An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias.

              In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 September 2020
                15 October 2020
                : 29
                : 157
                : 200165
                Affiliations
                [1 ]Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Dept of Medicine, New York, NY, USA
                [2 ]School of Medicine, Trinity College Dublin and Tallaght University Hospital, Dublin, Ireland
                [3 ]Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Dépt de Pharmacologie, CIC 1401, Bordeaux, France
                [4 ]INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC 1401, Bordeaux, France
                [5 ]National Heart and Lung Institute, Imperial College, London, UK
                Author notes
                Peter J. Barnes, National Heart and Lung Institute, Dovehouse St, London, SW3 6LY, UK. E-mail: p.j.barnes@ 123456imperial.ac.uk
                Author information
                https://orcid.org/0000-0001-5301-9926
                Article
                ERR-0165-2020
                10.1183/16000617.0165-2020
                9488551
                33060165
                6246c805-9d66-4d61-9f7f-107b28be04b7
                Copyright ©ERS 2020.

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 27 May 2020
                : 25 September 2020
                Categories
                Lung Science Conference
                10

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