Casanovas Albert, Sprenger Richard R, Tarasov Kirill, Ruckerbauer David E, Hannibal-Bach Hans Kristian, Zanghellini Jürgen, Jensen Ole N, Ejsing Christer S
Department of Biochemistry and Molecular Biology, VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, 5230 Odense, Denmark.
Département de Biochimie, Université de Montréal, Succ. Centre-Ville, 6128 Montreal, Quebec H3C 3J7, Canada.
Chem Biol. 2015 Mar 19;22(3):412-25. doi: 10.1016/j.chembiol.2015.02.007.
Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level.
阐明在不断变化的条件下脂质代谢如何以及在何种程度上发生重塑，对于理解细胞生理学至关重要。在此，我们分析了蛋白质组和脂质组动力学，以研究在酵母生理适应过程中，全球范围内脂质代谢的调节如何支持细胞结构和过程的重塑。我们的结果表明，心磷脂合成和重塑的激活在从发酵代谢向呼吸代谢的转变中支持线粒体生物发生；从头合成固醇机制的下调促使呼吸生长期间脂滴相关三酰甘油和固醇酯的差异周转；鞘脂代谢以先前未被认识的生长阶段特异性方式受到调节；并且不饱和脂肪酸的内源性合成通过异源二聚体Oaf1/Pip2转录因子构成过氧化物酶体生物发生的体内上游激活剂。我们的工作证明了脂质代谢在适应性过程中的关键作用，并提供了一个在细胞水平上研究其调节的资源。
