期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
卷 1839, 期 11, 页码 1217-1225出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagrm.2014.07.013
关键词
IFN gamma; Mitochondrial citrate carrier; NFkB; Pro-inflammatory cytokine; STAT1; TNF alpha
资金
- Minister dell'Universita e della Ricerca (MIUR) [20109Z2XRJ 009]
- Comitato Telethon Fondazione Onlus [GGP11139]
- Center of Excellence in Genomics (CEGBA)
- Italian Human Proteome Net [RBRN07BMCT_009]
The chronic induction of inflammation underlies multiple pathological conditions, including metabolic, autoimmune disorders and cancer. The mitochondrial citrate carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from the mitochondria to the cytoplasm, a process that profoundly influences energy balance in the cells. We have previously shown that SLC25A1 is a target gene for lipopolysaccharide signaling and promotes the production of inflammatory mediators. We now demonstrate that SLC25A1 is induced at the transcriptional level by two key pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma), and such induction involves the activity of the nuclear factor kappa B and STAT1 transcription factors. By studying the down-stream events following SLC25A1 activation during signals that mimic inflammation, we demonstrate that CIC is required for regulating the levels of nitric oxide and of prostaglandins by TNF alpha or IFN gamma. Importantly, we show that the citrate exported from mitochondria via CIC and its downstream metabolic intermediate, acetyl-coenzyme A, are necessary for TNF alpha or IFN gamma to induce nitric oxide and prostaglandin production. These findings provide the first line of evidence that the citrate export pathway, via CIC, is central for cytokine-induced inflammatory signals and shed new light on the relationship between energy metabolism and inflammation. (C) 2014 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据