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Complex regulation of mitochondrial signaling by human adenovirus

ABSTRACT: The controlled release of mitochondrial content has emerged as a key step in mitochondrial signaling. Particularly the release of mitochondrial DNA (mtDNA) into the cytosol has been shown to activate interferon beta (IFN-β) gene expression to execute the innate immune response. In this report, we show that human adenovirus type 5 (HAdV-C5) induces the release of mtDNA in infected cells. The release of mtDNA is mediated by the viral internal minor capsid protein pVI, which localizes into mitochondria and undergoes mitochondria-specific proteolytic processing. The membrane lytic activity of the pVI and the presence of the mitochondrial membrane proteins Bak and Bax are needed for the mtDNA release. Surprisingly, the pVI-mediate mtDNA release did not increase but blocked IFN-β gene expression. This inhibition was due to the concurrent leakage of the mitochondrial chaperon protein HSP60, which by inhibiting phosphorylation of the interferon regulatory factor 3 (IRF3), blocked IFN-β gene expression. Collectively, our study suggests that the complex release of mtDNA and mitochondrial proteins modulate the IFN-β signaling cascade during pathogenic HAdV-C5 infection.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Hela Cell

SUBMITTER: Mårten Larsson

LAB HEAD: Tanel Punga

PROVIDER: PXD043440 | Pride | 2024-05-27

REPOSITORIES: Pride

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			Action	DRS
	221216_Ctrl_1A_1.raw	Raw
	221216_Ctrl_1A_2.raw	Raw
	221216_Ctrl_1B_1.raw	Raw
	221216_Ctrl_1B_2.raw	Raw
	221216_Ctrl_1C_1.raw	Raw

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