2026-06-14T03:54:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/273392026-03-21T01:17:08Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Dunphy, Gillian
author
Adán-Barrientos, Irene
author
Fernández-Delgado, Irene
author
Villarroya-Beltri, Carolina
author
Heras-Murillo, Ignacio
author
Moya-Ruiz, Elena
author
Sánchez-Álvarez, Miguel
author
Jarit-Cabanillas, Aitor
author
Del Pozo, Miguel A
author
Guerra, Susana
author
Sánchez-Madrid, Francisco
author
Sancho, David
2026-03-20T10:21:43Z
2026-03-20T10:21:43Z
2026-02-10
Immunity. 2026 Feb 10;59(2):306-321.
Immunity
41610845
https://hdl.handle.net/20.500.12105/27339
Macrophage metabolism is intricately linked to cellular function. Contrasting with Toll-like receptor (TLR) stimulation, cytosolic nucleic acid sensing induced a decrease in mitochondrial membrane potential (MMP) while maintaining mitochondrial respiration. Interferon α/β (IFN-I) receptor (IFNAR) signaling was necessary and sufficient for this metabolic response. IFNAR signaling induced interferon-stimulated gene 15 (ISG15) expression and ISGylation of mitochondrial proteins, including subunits of mitochondrial complex V, increasing ATP production and decreasing MMP, thus enhancing macrophage efferocytic capacity. Moreover, the IFNAR-ISG15-mediated drop in MMP activated the mitochondrial protease OMA1, inducing mitochondrial fission and decreasing endoplasmic reticulum-mitochondria communication, thus dampening IFN-stimulated gene (ISG) induction. Loss of ISG15 or OMA1 enhanced histone acetylation and ISG induction upon IFN-I stimulation, in a manner dependent on mitochondrial calcium uptake. This increase in ISG induction provided protection against acute viral infections. These data indicate that IFNAR-ISG15 signaling boosts efferocytosis while limiting ISG induction, thereby promoting the resolution of inflammation.
eng
efferocytosis
interferon-stimulated genes
macrophage
metabolism
mitochondrial endoplasmic reticulum contacts
mitochondrial fission
mitochondrial membrane potential
oxidative phosphorylation
type I interferon
viral infection
A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages.
research article
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URL
https://repisalud.isciii.es/bitstreams/addcef1c-cb7f-4ee5-9ba7-c22c9114e8c0/download
File
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eb8385b7cfad5a34293ea50bec09347a
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application/pdf
A type I interferon-mitochondrial_Immunity_2026.pdf