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首页> 外文期刊>Nature Communications >Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk
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Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk

机译：乙酰-CoA通量调节蛋白质组和乙酰蛋白，保持细胞内代谢串扰

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摘要

AT-1/SLC33A1 is a key member of the endoplasmic reticulum (ER) acetylation machinery, transporting acetyl-CoA from the cytosol into the ER lumen where acetyl-CoA serves as the acetyl-group donor for Nε-lysine acetylation. Dysfunctional ER acetylation, as caused by heterozygous or homozygous mutations as well as gene duplication events of AT-1/SLC33A1, has been linked to both developmental and degenerative diseases. Here, we investigate two models of AT-1 dysregulation and altered acetyl-CoA flux: AT-1supS113R/+/sup mice, a model of AT-1 haploinsufficiency, and AT-1 sTg mice, a model of AT-1 overexpression. The animals display distinct metabolic adaptation across intracellular compartments, including reprogramming of lipid metabolism and mitochondria bioenergetics. Mechanistically, the perturbations to AT-1-dependent acetyl-CoA flux result in global and specific changes in both the proteome and the acetyl-proteome (protein acetylation). Collectively, our results suggest that AT-1 acts as an important metabolic regulator that maintains acetyl-CoA homeostasis by promoting functional crosstalk between different intracellular organelles.
机译：AT-1 / SLC33A1是内质网（ER）乙酰化机械的关键构件，将乙酰-CoA从细胞溶溶胶输送到ER腔中，其中乙酰-COA用作Nε-赖氨酸乙酰化的乙酰基供体。通过杂合或纯合突变引起的功能障碍ER乙酰化以及AT-1 / SLC33A1的基因重复事件已与发育和退行性疾病联系起来。在这里，我们研究了两种型号的AT-1呼吸缺乏率和改变的乙酰-COA通量：AT-1 S113R / + 小鼠，A型AT-1张不足功能，以及AT-1 STG小鼠，模型AT-1过表达。这些动物显示细胞内隔室的不同代谢适应，包括重编程脂质代谢和线粒体生物能器。机械地，在蛋白酶组和乙酰蛋白组（蛋白质乙酰化）中，对依赖于1-依赖性乙酰基-CoA通量的扰动导致全局和特异性变化。统称，我们的结果表明，AT-1作为重要的代谢调节剂，通过促进不同细胞内细胞器之间的功能性串扰来维持乙酰CoA稳态。

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