Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production

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http://hdl.handle.net/10138/238496

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Amini , P , Stojkov , D , Felser , A , Jackson , C B , Courage , C , Schaller , A , Gelman , L , Soriano , M E , Nuoffer , J-M , Scorrano , L , Benarafa , C , Yousefi , S & Simon , H-U 2018 , ' Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production ' , Nature Communications , vol. 9 , 2958 . https://doi.org/10.1038/s41467-018-05387-y

Titel: Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production
Författare: Amini, Poorya; Stojkov, Darko; Felser, Andrea; Jackson, Christopher B.; Courage, Carolina; Schaller, Andre; Gelman, Laurent; Soriano, Maria Eugenia; Nuoffer, Jean-Marc; Scorrano, Luca; Benarafa, Charaf; Yousefi, Shida; Simon, Hans-Uwe
Upphovmannens organisation: Anu Wartiovaara / Principal Investigator
Research Programme for Molecular Neurology
Research Programs Unit
University of Helsinki
Datum: 2018-07-27
Språk: eng
Sidantal: 16
Tillhör serie: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-05387-y
Permanenta länken (URI): http://hdl.handle.net/10138/238496
Abstrakt: Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1(N Delta)), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD(+) availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1(N Delta) mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.
Subject: DOMINANT OPTIC ATROPHY
MITOCHONDRIAL-DNA
OPA1 MUTATIONS
BACTERIAL CLEARANCE
SKELETAL-MUSCLE
NADPH OXIDASE
FUSION
RELEASE
DEGRANULATION
METABOLISM
3111 Biomedicine
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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