Accumulation of damaged mitochondria in alveolar macrophages with reduced OXPHOS related gene expression in IPF
Identifieur interne : 000B18 ( Main/Exploration ); précédent : 000B17; suivant : 000B19Accumulation of damaged mitochondria in alveolar macrophages with reduced OXPHOS related gene expression in IPF
Auteurs : Eliza Tsitoura ; Eirini Vasarmidi [Grèce] ; Eleni Bibaki ; Athina Trachalaki [Grèce] ; Chara Koutoulaki ; George Papastratigakis ; Sevasti Papadogiorgaki [Grèce] ; George Chalepakis [Grèce] ; Nikos Tzanakis [Grèce] ; Katerina M. Antoniou [Grèce]Source :
- Respiratory Research [ 1465-9921 ] ; 2019.
Abstract
Impaired mitochondria homeostasis and function are established hallmarks of aging and increasing evidence suggests a link with lung fibrosis. Mitochondria homeostasis may be also affected in alveolar macrophages (AMs) in idiopathic pulmonary fibrosis (IPF). In this study, we used bronchoalveolar lavage (BAL), a tool for both clinical and research purposes, and a rich source of AMs.
BAL samples were examined from 52 patients with IPF and 19 healthy individuals. Measurements of mitochondria reactive oxygen species (mtROS), mitochondria morphology and related gene expression were performed. Additionally, autophagy and mitophagy levels were analysed.
Mitochondria in AMs from IPF patients had prominent morphological defects and impaired transcription paralleled to a significant reduction of mitochondria homeostasis regulators PINK1, PARK2 and NRF1. mtROS, was significantly higher in IPF and associated with reduced expression of mitochondria-encoded oxidative phosphorylation (OXPHOS) genes. Age and decline in lung function correlated with higher mtROS levels. Augmentation of damaged, oxidised mitochondria in IPF AMs however was not coupled to increased macroautophagy and mitophagy, central processes in the maintenance of healthy mitochondria levels.
Our results suggest a perturbation of mitochondria homeostasis in alveolar macrophages in IPF.
Url:
DOI: 10.1186/s12931-019-1196-6
PubMed: 31775876
PubMed Central: 6880424
Affiliations:
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Eirini" sort="Vasarmidi, Eirini" uniqKey="Vasarmidi E" first="Eirini" last="Vasarmidi">Eirini Vasarmidi</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, Medical School,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.412481.a</institution-id><institution>Department of Respiratory Medicine,</institution><institution>University Hospital of Heraklion,</institution></institution-wrap>Heraklion, Greece</nlm:aff><country 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3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, Medical School,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.412481.a</institution-id><institution>Department of Respiratory Medicine,</institution><institution>University Hospital of Heraklion,</institution></institution-wrap>Heraklion, Greece</nlm:aff><country xml:lang="fr">Grèce</country><wicri:regionArea>Heraklion</wicri:regionArea></affiliation></author><author><name sortKey="Koutoulaki, Chara" sort="Koutoulaki, Chara" uniqKey="Koutoulaki C" first="Chara" last="Koutoulaki">Chara Koutoulaki</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, Medical School,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation></author><author><name sortKey="Papastratigakis, George" sort="Papastratigakis, George" uniqKey="Papastratigakis G" first="George" last="Papastratigakis">George Papastratigakis</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, Medical School,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation></author><author><name sortKey="Papadogiorgaki, Sevasti" sort="Papadogiorgaki, Sevasti" uniqKey="Papadogiorgaki S" first="Sevasti" last="Papadogiorgaki">Sevasti Papadogiorgaki</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Electron Microscopy Laboratory,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Greece</nlm:aff><country xml:lang="fr">Grèce</country><wicri:regionArea>Heraklion</wicri:regionArea></affiliation></author><author><name sortKey="Chalepakis, George" sort="Chalepakis, George" uniqKey="Chalepakis G" first="George" last="Chalepakis">George Chalepakis</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Electron Microscopy Laboratory,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Greece</nlm:aff><country xml:lang="fr">Grèce</country><wicri:regionArea>Heraklion</wicri:regionArea></affiliation></author><author><name sortKey="Tzanakis, Nikos" sort="Tzanakis, Nikos" uniqKey="Tzanakis N" first="Nikos" last="Tzanakis">Nikos Tzanakis</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, Medical School,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.412481.a</institution-id><institution>Department of Respiratory Medicine,</institution><institution>University Hospital of Heraklion,</institution></institution-wrap>Heraklion, Greece</nlm:aff><country xml:lang="fr">Grèce</country><wicri:regionArea>Heraklion</wicri:regionArea></affiliation></author><author><name sortKey="Antoniou, Katerina M" sort="Antoniou, Katerina M" uniqKey="Antoniou K" first="Katerina M." last="Antoniou">Katerina M. Antoniou</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0576 3437</institution-id><institution-id institution-id-type="GRID">grid.8127.c</institution-id><institution>Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pneumonology, Medical School,</institution><institution>University of Crete,</institution></institution-wrap>Heraklion, Crete Greece</nlm:aff><wicri:noCountry code="subfield">Crete Greece</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.412481.a</institution-id><institution>Department of Respiratory Medicine,</institution><institution>University Hospital of Heraklion,</institution></institution-wrap>Heraklion, Greece</nlm:aff><country xml:lang="fr">Grèce</country><wicri:regionArea>Heraklion</wicri:regionArea></affiliation></author></analytic><series><title level="j">Respiratory Research</title><idno type="ISSN">1465-9921</idno><idno type="eISSN">1465-993X</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">Impaired mitochondria homeostasis and function are established hallmarks of aging and increasing evidence suggests a link with lung fibrosis. Mitochondria homeostasis may be also affected in alveolar macrophages (AMs) in idiopathic pulmonary fibrosis (IPF). In this study, we used bronchoalveolar lavage (BAL), a tool for both clinical and research purposes, and a rich source of AMs.</p></sec><sec><title>Methods</title><p id="Par2">BAL samples were examined from 52 patients with IPF and 19 healthy individuals. Measurements of mitochondria reactive oxygen species (mtROS), mitochondria morphology and related gene expression were performed. Additionally, autophagy and mitophagy levels were analysed.</p></sec><sec><title>Results</title><p id="Par3">Mitochondria in AMs from IPF patients had prominent morphological defects and impaired transcription paralleled to a significant reduction of mitochondria homeostasis regulators PINK1, PARK2 and NRF1. mtROS, was significantly higher in IPF and associated with reduced expression of mitochondria-encoded oxidative phosphorylation (OXPHOS) genes. Age and decline in lung function correlated with higher mtROS levels. Augmentation of damaged, oxidised mitochondria in IPF AMs however was not coupled to increased macroautophagy and mitophagy, central processes in the maintenance of healthy mitochondria levels.</p></sec><sec><title>Conclusion</title><p id="Par4">Our results suggest a perturbation of mitochondria homeostasis in alveolar macrophages in IPF.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Richeldi, L" uniqKey="Richeldi L">L Richeldi</name></author><author><name sortKey="Collard, Hr" uniqKey="Collard H">HR Collard</name></author><author><name sortKey="Jones, Mg" uniqKey="Jones M">MG Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wuyts, Wa" uniqKey="Wuyts W">WA Wuyts</name></author><author><name sortKey="Agostini, C" uniqKey="Agostini C">C Agostini</name></author><author><name sortKey="Antoniou, Km" uniqKey="Antoniou K">KM Antoniou</name></author><author><name sortKey="Bouros, D" uniqKey="Bouros D">D Bouros</name></author><author><name sortKey="Chambers, Rc" uniqKey="Chambers R">RC Chambers</name></author><author><name sortKey="Cottin, V" uniqKey="Cottin V">V Cottin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zank, Dc" uniqKey="Zank D">DC Zank</name></author><author><name sortKey="Bueno, M" uniqKey="Bueno M">M Bueno</name></author><author><name sortKey="Mora, Al" uniqKey="Mora A">AL Mora</name></author><author><name sortKey="Rojas, M" uniqKey="Rojas M">M Rojas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Angajala, A" uniqKey="Angajala A">A Angajala</name></author><author><name sortKey="Lim, S" uniqKey="Lim S">S Lim</name></author><author><name sortKey="Phillips, Jb" uniqKey="Phillips J">JB Phillips</name></author><author><name sortKey="Kim, J H" uniqKey="Kim J">J-H Kim</name></author><author><name sortKey="Yates, C" uniqKey="Yates C">C Yates</name></author><author><name sortKey="You, 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uniqKey="Cho S">SJ Cho</name></author><author><name sortKey="Harris, Rm" uniqKey="Harris R">RM Harris</name></author><author><name sortKey="Huang, Hr" uniqKey="Huang H">HR Huang</name></author><author><name sortKey="Yun, Hs" uniqKey="Yun H">HS Yun</name></author><author><name sortKey="Schiffer, Kt" uniqKey="Schiffer K">KT Schiffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Lu, F" uniqKey="Lu F">F Lu</name></author><author><name sortKey="Kang, L" uniqKey="Kang L">L Kang</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Grèce</li></country></list><tree><noCountry><name sortKey="Bibaki, Eleni" sort="Bibaki, Eleni" uniqKey="Bibaki E" first="Eleni" last="Bibaki">Eleni Bibaki</name><name sortKey="Koutoulaki, Chara" sort="Koutoulaki, Chara" uniqKey="Koutoulaki C" first="Chara" last="Koutoulaki">Chara Koutoulaki</name><name sortKey="Papastratigakis, George" sort="Papastratigakis, George" uniqKey="Papastratigakis G" first="George" last="Papastratigakis">George Papastratigakis</name><name sortKey="Tsitoura, Eliza" sort="Tsitoura, Eliza" uniqKey="Tsitoura E" first="Eliza" last="Tsitoura">Eliza Tsitoura</name></noCountry><country name="Grèce"><noRegion><name sortKey="Vasarmidi, Eirini" sort="Vasarmidi, Eirini" uniqKey="Vasarmidi E" first="Eirini" last="Vasarmidi">Eirini Vasarmidi</name></noRegion><name sortKey="Antoniou, Katerina M" sort="Antoniou, Katerina M" uniqKey="Antoniou K" first="Katerina M." last="Antoniou">Katerina M. Antoniou</name><name sortKey="Chalepakis, George" sort="Chalepakis, George" uniqKey="Chalepakis G" first="George" last="Chalepakis">George Chalepakis</name><name sortKey="Papadogiorgaki, Sevasti" sort="Papadogiorgaki, Sevasti" uniqKey="Papadogiorgaki S" first="Sevasti" last="Papadogiorgaki">Sevasti Papadogiorgaki</name><name sortKey="Trachalaki, Athina" sort="Trachalaki, Athina" uniqKey="Trachalaki A" first="Athina" last="Trachalaki">Athina Trachalaki</name><name sortKey="Tzanakis, Nikos" sort="Tzanakis, Nikos" uniqKey="Tzanakis N" first="Nikos" last="Tzanakis">Nikos Tzanakis</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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