小柯机器人

美国杜克大学医学中心Deborah M. Muoio研究组发现，肌肉线粒体乙酰赖氨酸代谢的中断，可促进胰岛素耐受和氧化还原应激，但无明显的呼吸功能障碍。该成果2019年12月5日在线发表在《细胞—代谢》上。

这项研究试图使用双敲除（DKO）小鼠模型鉴定线粒体蛋白乙酰化的功能重要性，该模型在肉毒碱乙酰转移酶和Sirtuin 3的遗传切除作用下在乙酰辅酶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耐受的形成更为严重。

但是，超乙酰化的DKO线粒体的功能表型在很大程度上是正常的。在鉴定的超过120种呼吸功能试验中，乙酰赖氨酸水平显著升高后，观察到的最一致特征是脂肪酸燃料中的氧通量增加和电子泄漏率升高。总之，这些发现挑战了赖氨酸乙酰化对线粒体质量和性能造成广泛损害的观点，并提出了乙酰赖氨酸周转率而非乙酰赖氨酸化学计量改变调节氧化还原平衡和碳通量的可能性。

附：英文原文

Title: Disruption of Acetyl-Lysine Turnover in Muscle Mitochondria Promotes Insulin Resistance and Redox Stress without Overt Respiratory Dysfunction

Author: Ashley S. Williams, Timothy R. Koves, Michael T. Davidson, Scott B. Crown, Kelsey H. Fisher-Wellman, Maria J. Torres, James A. Draper, Tara M. Narowski, Dorothy H. Slentz, Louise Lantier, David H. Wasserman, Paul A. Grimsrud, Deborah M. Muoio

Issue&Volume: December 05, 2019

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

DOI: 10.1016/j.cmet.2019.11.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30610-2

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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