Mitochondrial fusion mediator optic atrophy 1 as regulator of cell metabolism in macrophages
Abstract: Residing at the inner mitochondrial membrane, optic atrophy 1 (Opa1) constitutes a prominent regulator of mitochondrial morphology. It executes fusion of inner mitochondrial membranes, yet it also influences electron transport chain activity and mitochondrial genome maintenance. Only recently, Opa1 was discovered to interfere with complex immunologic processes in immune cells. In macrophages, rewiring of immune function is closely intertwined with alterations in mitochondrial morphology and cell metabolism. Whereas the connection between cell metabolism and immune function in macrophages receives extensive review, it remains unclear how mitochondrial morphology links to macrophage metabolism and function. To investigate whether mitochondrial fusion mediator Opa1 influences cell metabolism and immune function of macrophages, I generated Opa1-deficient primary mouse macrophages using a Cx3cr1-Cre/loxP system. Confocal fluorescence image analysis and flow cytometry revealed that Opa1-deficient primary mouse macrophages exhibited small and highly spherical mitochondria without changes in mitochondrial volume per cell. Extracellular metabolic flux analysis showed that cells were less prone to engage in oxidative phosphorylation, but instead relied heavily on glycolysis and lactic acid fermentation. Labelled carbon tracing identified glutamine as main source to fuel tricarboxylic acid cycle in Opa1-deficient macrophages. While causing profound alterations in macrophage metabolism, Opa1 deficiency did not lead to a manifest defect in macrophage polarisation as assessed by flow cytometric analysis of polarisation markers and cytokines. Immunofluorescence analysis of tissue-resident macrophage populations revealed a detrimental effect of Opa1 deficiency on splenic marginal metallophillic macrophages. In summary, Opa1 deficiency caused a profound metabolic rewiring in macrophages, which remained, however, uncoupled from macrophage phenotype and polarisation capacity
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Universität Freiburg, Dissertation, 2023
- Schlagwort
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Makrophage
Mitochondrium
Immunreaktion
Mitochondrium
Monozyten-Makrophagen-System
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2023
- Urheber
- Beteiligte Personen und Organisationen
- DOI
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10.6094/UNIFR/237183
- URN
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urn:nbn:de:bsz:25-freidok-2371830
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:45 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
Entstanden
- 2023
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