Department of Molecular Biology and the Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Rep. 2018 Jun 26;23(13):3701-3709. doi: 10.1016/j.celrep.2018.05.058.
Micropeptide regulator of β-oxidation (MOXI) is a conserved muscle-enriched protein encoded by an RNA transcript misannotated as non-coding. MOXI localizes to the inner mitochondrial membrane where it associates with the mitochondrial trifunctional protein, an enzyme complex that plays a critical role in fatty acid β-oxidation. Isolated heart and skeletal muscle mitochondria from MOXI knockout mice exhibit a diminished ability to metabolize fatty acids, while transgenic MOXI overexpression leads to enhanced β-oxidation. Additionally, hearts from MOXI knockout mice preferentially oxidize carbohydrates over fatty acids in an isolated perfused heart system compared to wild-type (WT) animals. MOXI knockout mice also exhibit a profound reduction in exercise capacity, highlighting the role of MOXI in metabolic control. The functional characterization of MOXI provides insight into the regulation of mitochondrial metabolism and energy homeostasis and underscores the regulatory potential of additional micropeptides that have yet to be identified.
β-氧化调节微肽（MOXI）是一种保守的肌肉丰富蛋白，由 RNA 转录本编码，该转录本被错误注释为非编码。MOXI 定位于线粒体内膜，与三功能蛋白（mitochondrial trifunctional protein）结合，后者是在脂肪酸β-氧化中起关键作用的酶复合物。从 MOXI 敲除小鼠的分离心脏和骨骼肌线粒体中，脂肪酸代谢能力降低，而转基因 MOXI 过表达导致β-氧化增强。此外，与野生型（WT）动物相比，在分离的灌注心脏系统中，MOXI 敲除小鼠的心脏优先氧化碳水化合物而不是脂肪酸。MOXI 敲除小鼠的运动能力也显著降低，这凸显了 MOXI 在代谢控制中的作用。MOXI 的功能特征为线粒体代谢和能量稳态的调节提供了深入了解，并强调了其他尚未确定的微肽的调节潜力。
