Sterol transport and cell-cycle requirements for isoprenoids

胆固醇是一种必要的邪恶。胆固醇过多会导致疾病，但一些胆固醇仍然是细胞正常生长所必需的。胆固醇和相关的脂类是包裹细胞的膜结构所必需的，而胆固醇影响嵌入膜内的蛋白质的功能。除了在我们体内运输胆固醇的运输机制外，胆固醇还必须在细胞内部运输。胆固醇如何在细胞内移动的机制还知之甚少。OSBP相关蛋白(ORPs)与胆固醇在细胞内的运输有关，但这些蛋白如何完成这一功能仍存在争议。我们选择了研究酵母细胞中与胆固醇相关的甾醇的运输和ORPs，这可以很容易地利用各种分子遗传技术来开发。酵母也代表了我们自身细胞的简单版本，所以我们在酵母中学到的东西可以应用于人类细胞中胆固醇运输的研究。我们工作的目标是定义胆固醇在细胞内的运输方式，并了解胆固醇及其生物合成前体如何影响细胞生长和分裂。

Cholesterol is a necessary evil. Too much cholesterol leads to disease, but some cholesterol is nonetheless needed for normal cell growth. Cholesterol and related lipids are required for the structure of the membrane that envelopes cells, and cholesterol affects the function of proteins embedded within this membrane. In addition to the transport mechanisms that move cholesterol through our bodies, cholesterol must also be transported within the cell interior. The mechanism for how cholesterol moves within cells is poorly understood. OSBP-related proteins (ORPs) are implicated in the transport of cholesterol within cells, but how these proteins might accomplish that function is controversial. We have chosen to study ORPs and the transport of cholesterol-related sterols in yeast cells, which can be easily exploited using a large variety of molecular genetic techniques. Yeast also represent simple versions of our own cells, so what we learn in yeast can be applied to studies of cholesterol transport in human cells. The goal of our work is to define how cholesterol is transported within cells, and to understand how cholesterol and its biosynthetic precursors affect cell growth and division.