Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Am J Pathol. 2009 Nov;175(5):1810-6. doi: 10.2353/ajpath.2009.090219. Epub 2009 Oct 15.
Presenilin-1 (PS1) and -2 (PS2), which when mutated cause familial Alzheimer disease, have been localized to numerous compartments of the cell, including the endoplasmic reticulum, Golgi, nuclear envelope, endosomes, lysosomes, the plasma membrane, and mitochondria. Using three complementary approaches, subcellular fractionation, gamma-secretase activity assays, and immunocytochemistry, we show that presenilins are highly enriched in a subcompartment of the endoplasmic reticulum that is associated with mitochondria and that forms a physical bridge between the two organelles, called endoplasmic reticulum-mitochondria-associated membranes. A localization of PS1 and PS2 in mitochondria-associated membranes may help reconcile the disparate hypotheses regarding the pathogenesis of Alzheimer disease and may explain many seemingly unrelated features of this devastating neurodegenerative disorder.
早老素蛋白 1（PS1）和 2（PS2），当发生突变时会导致家族性阿尔茨海默病，已被定位到细胞的许多隔室中，包括内质网、高尔基体、核膜、内体、溶酶体、质膜和线粒体。我们使用三种互补的方法，亚细胞分级分离、γ-分泌酶活性测定和免疫细胞化学，表明早老素蛋白在与线粒体相关的内质网的一个亚隔室中高度富集，该亚隔室形成了两个细胞器之间的物理桥，称为内质网-线粒体相关膜。PS1 和 PS2 在线粒体相关膜中的定位可能有助于调和关于阿尔茨海默病发病机制的不同假说，并可能解释这种破坏性神经退行性疾病的许多看似无关的特征。
