This study sought to examine the functional significance of mitochondrial protein acetylation using a double knockout (DKO) mouse model harboring muscle-specific deficits in acetyl-CoA buffering and lysine deacetylation, due to genetic ablation of carnitine acetyltransferase and Sirtuin 3, respectively. DKO mice are highly susceptible to extreme hyperacetylation of the mitochondrial proteome and develop a more severe form of diet-induced insulin resistance than either single KO mouse line. However, the functional phenotype of hyperacetylated DKO mitochondria is largely normal. Of the >120 measures of respiratory function assayed, the most consistently observed traits of a markedly heightened acetyl-lysine landscape are enhanced oxygen flux in the context of fatty acid fuel and elevated rates of electron leak. In sum, the findings challenge the notion that lysine acetylation causes broad-ranging damage to mitochondrial quality and performance and raise the possibility that acetyl-lysine turnover, rather than acetyl-lysine stoichiometry, modulates redox balance and carbon flux.

中文翻译：

---

肌线粒体中乙酰赖氨酸转换的中断促进胰岛素抵抗和氧化还原应激而没有明显的呼吸功能障碍。

这项研究试图使用双敲除（DKO）小鼠模型检查线粒体蛋白乙酰化的功能重要性，该模型在肉碱乙酰基转移酶和Sirtuin 3的基因消融作用下，在乙酰辅酶A缓冲和赖氨酸脱乙酰化中具有肌肉特异性缺陷。DKO小鼠极易受到线粒体蛋白质组极端过度乙酰化的影响，与任何一种KO小鼠相比，其饮食诱导的胰岛素抵抗的形式更为严重。但是，过度乙酰化的DKO线粒体的功能表型在很大程度上是正常的。在分析的> 120种呼吸功能测量中，乙酰赖氨酸水平显着升高的最一致观察到的特征是脂肪酸燃料中的氧通量增加和电子泄漏率升高。总共，