Zanni Elena, Farina Francesca, Ricci Antonella, Mancini Patrizia, Frank Claudio, Palleschi Claudio, Uccelletti Daniela
Dpt, Developmental and Cell Biology, University LA SAPIENZA, P.le. A. Moro, 500185 Rome, Italy.
BMC Cell Biol. 2009 Dec 14;10:86. doi: 10.1186/1471-2121-10-86.
Protein N-glycosylation is a relevant metabolic pathway in eukaryotes and plays key roles in cell processes. In yeasts, outer chain branching is initiated in the Golgi apparatus by the alpha-1,6-mannosyltransferase Och1p.
Here we report that, in Kluyveromyces lactis, this glycosyltransferase is also required to maintain functional mitochondria and calcium homeostasis. Cells carrying a mutation in KlOCH1 gene showed altered mitochondrial morphology, increased accumulation of ROS and reduced expression of calcium signalling genes such as calmodulin and calcineurin. Intracellular calcium concentration was also reduced in the mutant cells with respect to the wild type counterparts.Phenotypes that occur in cells lacking the alpha-1,6-mannosyltransferase, including oxidative stress and impaired mitochondria functionality, were suppressed by increased dosage of KlCmd1p. This, in turn, acts through the action of calcineurin.
Proper functioning of the alpha-1,6-mannosyltransferase in the N-glycosylation pathway of K. lactis is required for maintaining normal calcium homeostasis; this is necessary for physiological mitochondria dynamics and functionality.
蛋白质N-糖基化是真核生物中一种重要的代谢途径，在细胞过程中发挥关键作用。在酵母中，外链分支由α-1,6-甘露糖基转移酶Och1p在高尔基体中启动。
我们在此报告，在乳酸克鲁维酵母中，这种糖基转移酶对于维持功能性线粒体和钙稳态也是必需的。携带KlOCH1基因突变的细胞表现出线粒体形态改变、活性氧积累增加以及钙信号基因（如钙调蛋白和钙神经素）的表达降低。与野生型细胞相比，突变细胞中的细胞内钙浓度也降低了。缺乏α-1,6-甘露糖基转移酶的细胞中出现的表型，包括氧化应激和线粒体功能受损，通过增加KlCmd1p的剂量得以抑制。这反过来又通过钙神经素的作用发挥作用。
乳酸克鲁维酵母N-糖基化途径中α-1,6-甘露糖基转移酶的正常功能对于维持正常的钙稳态是必需的；这对于生理线粒体动态和功能是必要的。
