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Mitochondrial Membrane Potential Regulates Nuclear Gene Expression in Macrophages Exposed to Prostaglandin E2.

Abstract：

:Metabolic engagement is intrinsic to immune cell function. Prostaglandin E2 (PGE2) has been shown to modulate macrophage activation, yet how PGE2 might affect metabolism is unclear. Here, we show that PGE2 caused mitochondrial membrane potential (Δψm) to dissipate in interleukin-4-activated (M(IL-4)) macrophages. Effects on Δψm were a consequence of PGE2-initiated transcriptional regulation of genes, particularly Got1, in the malate-aspartate shuttle (MAS). Reduced Δψm caused alterations in the expression of 126 voltage-regulated genes (VRGs), including those encoding resistin-like molecule α (RELMα), a key marker of M(IL-4) cells, and genes that regulate the cell cycle. The transcription factor ETS variant 1 (ETV1) played a role in the regulation of 38% of the VRGs. These results reveal ETV1 as a Δψm-sensitive transcription factor and Δψm as a mediator of mitochondrial-directed nuclear gene expression.

journal_name

Immunity

journal_title

Immunity

authors

Sanin DE,Matsushita M,Klein Geltink RI,Grzes KM,van Teijlingen Bakker N,Corrado M,Kabat AM,Buck MD,Qiu J,Lawless SJ,Cameron AM,Villa M,Baixauli F,Patterson AE,Hässler F,Curtis JD,O'Neill CM,O'Sullivan D,Wu D,Mittler

doi

10.1016/j.immuni.2018.10.011

subject

Has Abstract

pub_date

2018-12-18 00:00:00

pages

1021-1033.e6

issue

6

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(18)30476-X

journal_volume

49

pub_type

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