Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, USA; Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Curr Biol. 2018 Oct 22;28(20):R1212-R1219. doi: 10.1016/j.cub.2018.08.022.
Biology students today are taught that mitochondria are 'the powerhouse of the cell'. This gross over-simplification of their cellular role has arguably led to a paucity of knowledge concerning the many other tasks carried out by this multifunctional organelle. Mitochondrial fatty acid synthesis (mtFAS) is one such under-appreciated pathway that is crucial for mitochondrial function, although even mitochondrial experts are often surprised to learn of its existence. For many years, the only function of mtFAS was thought to be the production of lipoic acid, an important co-factor for several mitochondrial enzymes. However, recent advances have revealed a far wider role for mtFAS in mitochondrial physiology. The discovery of human patients with mutations in mtFAS enzymes has brought renewed interest in understanding the full significance of this novel mode of mitochondrial metabolic regulation. We now appreciate that mtFAS is a nutrient-sensitive pathway that provides an elegant mechanism whereby acetyl-CoA regulates its own consumption via coordination of lipoic acid synthesis and tricarboxylic acid (TCA) cycle activity, iron-sulfur (FeS) cluster biogenesis, assembly of oxidative phosphorylation complexes, and mitochondrial translation. In this minireview, we describe and build upon the important discoveries that led to our current understanding of this elegant mechanism of coordination of nutrient status and metabolism.
今天的生物学学生被教导说线粒体是“细胞的动力源”。这种对其细胞作用的过分简化的理解，可以说导致了人们对这个多功能细胞器所执行的许多其他任务的知识匮乏。线粒体脂肪酸合成（mtFAS）就是这样一条被低估的途径，它对线粒体功能至关重要，尽管即使是线粒体专家也常常对其存在感到惊讶。多年来，mtFAS 的唯一功能被认为是产生硫辛酸，这是几种线粒体酶的重要辅酶。然而，最近的进展揭示了 mtFAS 在线粒体生理学中具有更广泛的作用。mtFAS 酶突变的人类患者的发现，重新引起了人们对理解这种新的线粒体代谢调节模式的全部意义的兴趣。我们现在意识到，mtFAS 是一种营养敏感途径，它提供了一种优雅的机制，通过协调硫辛酸合成和三羧酸（TCA）循环活性、铁硫（FeS）簇生物发生、氧化磷酸化复合物的组装以及线粒体翻译，乙酰辅酶 A 可以调节自身的消耗。在这篇迷你综述中，我们描述并扩展了导致我们目前对这种协调营养状况和代谢的优雅机制的理解的重要发现。
