促炎巨噬细胞的激活不需要氧化磷酸化的抑制。

IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2025-01-03 DOI:10.1038/s44319-024-00351-y
Andréa B Ball, Anthony E Jones, Kaitlyn B Nguyễn, Amy Rios, Nico Marx, Wei Yuan Hsieh, Krista Yang, Brandon R Desousa, Kristen K O Kim, Michaela Veliova, Zena Marie Del Mundo, Orian S Shirihai, Cristiane Benincá, Linsey Stiles, Steven J Bensinger, Ajit S Divakaruni
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引用次数: 0

摘要

促炎巨噬细胞活化是线粒体如何作为信号细胞器的一个标志性例子。氧化磷酸化在经典的巨噬细胞激活时急剧减少,因为线粒体被认为从ATP的产生转向积累信号,放大效应功能。然而,关于这种呼吸衰竭是必要的还是可有可无的,证据是相互矛盾的。在这里,我们系统地研究了这个问题,并表明氧化磷酸化的减少不是促炎巨噬细胞激活所必需的。不同的促炎刺激会对生物能量参数产生不同的影响,电子传递链抑制的药理学和遗传学模型显示呼吸和巨噬细胞激活之间没有因果关系。此外,信号代谢产物琥珀酸盐和衣康酸盐可以在小鼠和人巨噬细胞的TCA循环中独立积累,并且可以在不抑制氧化磷酸化的情况下激活腹膜巨噬细胞。结果表明,代谢表型具有可塑性,可以支持促炎巨噬细胞的激活。
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Pro-inflammatory macrophage activation does not require inhibition of oxidative phosphorylation.

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Oxidative phosphorylation sharply decreases upon classical macrophage activation, as mitochondria are thought to shift from ATP production towards accumulating signals that amplify effector function. However, evidence is conflicting regarding whether this collapse in respiration is essential or dispensable. Here we systematically examine this question and show that reduced oxidative phosphorylation is not required for pro-inflammatory macrophage activation. Different pro-inflammatory stimuli elicit varying effects on bioenergetic parameters, and pharmacologic and genetic models of electron transport chain inhibition show no causative link between respiration and macrophage activation. Furthermore, the signaling metabolites succinate and itaconate can accumulate independently of characteristic breaks in the TCA cycle in mouse and human macrophages, and peritoneal macrophages can be activated in vivo without inhibition of oxidative phosphorylation. The results indicate there is plasticity in the metabolic phenotypes that can support pro-inflammatory macrophage activation.

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来源期刊
EMBO Reports
EMBO Reports 生物-生化与分子生物学
CiteScore
11.20
自引率
1.30%
发文量
267
审稿时长
1 months
期刊介绍: EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry. 
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