Organelle size control systems: From cell geometry to organelle-directed medicine
Organelle size control systems: From cell geometry to organelle-directed medicine
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DOI：
10.1002/bies.201200043
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发表时间：
2012-09-01
期刊：
影响因子：
4
通讯作者：
Marshall, Wallace F.
中科院分区：
文献类型：
--
作者：
Marshall, Wallace F.
真核细胞器封装细胞生化途径的定义子集。例如，脂肪酸的β氧化发生在线粒体内，而脂肪酸链延长发生在内质网膜上。细胞器膜将反应相互隔离并储存中间体和产物，因此可以被视为“反应容器”，其作用类似于化学工厂的回流塔和储存罐。为了开发一个有效的化学制造过程，仅仅关注化学是不够的，即直接参与反应的反应物和溶剂。反应容器的尺寸和设计同样重要。同样，在细胞内，细胞器的大小将影响其中包含的生化途径的速率。细胞器表面积可以限制底物的输入速率和产物的流出，而细胞器的体积可以决定可以建立的中间体的数量（图1）。许多关键的代谢酶是细胞器膜蛋白，在这种情况下，增加的表面积可以允许更多的分子进入膜，以增加代谢通量。细胞器大小对代谢的影响表现在这样一个事实，即在专门用于某些途径的细胞中，包含这些途径的细胞器比其他细胞类型要大。分泌细胞是一个明显的例子，其中对分泌蛋白的高速率流动的需要通过内质网和高尔基体的大量过度增殖来满足。其他实例包括脂肪细胞中的脂滴增大、肠内衬细胞表面上的微绒毛增殖、视杆细胞与视锥细胞中含有视紫红质的囊泡的表面积和体积增加，以及线粒体丰度随呼吸状态而变化。
Eukaryotic organelles encapsulate defined subsets of cellular biochemical pathways. For example, beta oxidation of fatty acids occurs inside mitochondria while fatty acid chain elongation takes place on the endoplasmic reticulum membrane. Organelle membranes isolate reactions from each other and store intermediates and products, and can thus be viewed as “reaction vessels”, playing roles analogous to the reflux columns and holding tanks of a chemical factory. To develop an effective chemical manufacturing process, it is not enough to focus just on the chemistry, ie the reactants and solvents that directly participate in reactions. The size and design of the reaction vessels is of equal importance. Likewise, within a cell, the size of organelles will influence the rates of biochemical pathways contained within them. Organelle surface area can limit the rate of import of substrates and efflux of products, while the volume of the organelle can dictate the quantity of intermediates that can build up (Figure 1). Many key metabolic enzymes are organelle membrane proteins, and in such cases increased surface area could allow larger numbers of molecules into the membrane to increase metabolic flux.The influence of organelle size on metabolism is indicated by the fact that in cells specialized for certain pathways, the organelles that contain these pathways are enlarged compared to other cell types. Secretory cells are an obvious example, in which the requirement for a high rate of flux of secreted proteins is met by a massive over proliferation of endoplasmic reticulum and Golgi apparatus. Other examples include enlarged lipid droplets in adipose cells, proliferation of microvilli on the surface of cells lining the intestine, increased surface area and volume of rhodopsin containing vesicles in rods versus cones, and changes in mitochondrial abundance as a function of respiratory state.