Spincemaille Pieter, Matmati Nabil, Hannun Yusuf A, Cammue Bruno P A, Thevissen Karin
Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium.
Department of Medicine and the Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA.
Biochim Biophys Acta. 2014 Oct;1840(10):3131-7. doi: 10.1016/j.bbagen.2014.06.015. Epub 2014 Jun 25.
Sphingolipids (SLs) are not only key components of cellular membranes, but also play an important role as signaling molecules in orchestrating both cell growth and apoptosis. In Saccharomyces cerevisiae, three complex SLs are present and hydrolysis of either of these species is catalyzed by the inositol phosphosphingolipid phospholipase C (Isc1p). Strikingly, mutants deficient in Isc1p display several hallmarks of mitochondrial dysfunction such as the inability to grow on a non-fermentative carbon course, increased oxidative stress and aberrant mitochondrial morphology.
In this review, we focus on the pivotal role of Isc1p in regulating mitochondrial function via SL metabolism, and on Sch9p as a central signal transducer. Sch9p is one of the main effectors of the target of rapamycin complex 1 (TORC1), which is regarded as a crucial signaling axis for the regulation of Isc1p-mediated events. Finally, we describe the retrograde response, a signaling event originating from mitochondria to the nucleus, which results in the induction of nuclear target genes. Intriguingly, the retrograde response also interacts with SL homeostasis.
All of the above suggests a pivotal signaling role for SLs in maintaining correct mitochondrial function in budding yeast.
Studies with budding yeast provide insight on SL signaling events that affect mitochondrial function.
鞘脂（SLs）不仅是细胞膜的关键组成部分，而且作为信号分子在协调细胞生长和凋亡中发挥重要作用。在酿酒酵母中，存在三种复杂的鞘脂，这些鞘脂中的任何一种的水解都是由肌醇磷酸鞘脂磷脂酶C（Isc1p）催化的。引人注目的是，缺乏Isc1p的突变体表现出线粒体功能障碍的几个特征，如无法在非发酵碳源上生长、氧化应激增加和线粒体形态异常。
在本综述中，我们重点关注Isc1p在通过鞘脂代谢调节线粒体功能中的关键作用，以及作为中心信号转导分子的Sch9p。Sch9p是雷帕霉素复合物1（TORC1）靶点的主要效应器之一，TORC1被认为是调节Isc1p介导事件的关键信号轴。最后，我们描述了逆向反应，这是一种从线粒体到细胞核的信号事件，其导致核靶基因的诱导。有趣的是，逆向反应也与鞘脂稳态相互作用。
上述所有内容表明鞘脂在维持出芽酵母正确的线粒体功能中具有关键的信号作用。
对出芽酵母的研究为影响线粒体功能的鞘脂信号事件提供了见解。
