Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
J Alzheimers Dis. 2018;61(2):793-801. doi: 10.3233/JAD-170613.
The translocase of the outer membrane (TOM) is a vital mitochondrial transport system facilitating the importation of nuclear encoded proteins into the organelle. While mitochondrial dysfunction, including perturbation of oxidative phosphorylation (OXPHOS) complex, is evident in Alzheimer's disease (AD), it remains unclear whether the observed OXPHOS deficits may be associated with TOM alterations.
To correlate TOM subunits with OXPHOS complex proteins in AD.
Postmortem neocortex (BA40) from AD and age-matched controls were processed to obtain mitochondrial enriched homogenates for the measurement of Tom20, Tom22, Tom40, and Tom70 as well as components of OXPHOS complex I-V by immunoblotting.
Tom20 and Tom70 immunoreactivities were significantly reduced in AD, as were components of OXPHOS complex I and III. Both Tom20 and Tom70 positively correlated with complex III and V, while Tom20 also correlated withcomplex IV.
Reductions in certain TOM subunits and their correlations with specific OXPHOS complex proteins suggest that an impaired mitochondrial transportation system may contribute to previously observed oxidative phosphorylation deficits in AD. Follow-up studies are needed to corroborate the present correlative study.
外膜转位酶（TOM）是一种重要的线粒体运输系统，有助于将核编码蛋白导入细胞器。虽然阿尔茨海默病（AD）中存在线粒体功能障碍，包括氧化磷酸化（OXPHOS）复合物的扰动，但尚不清楚观察到的 OXPHOS 缺陷是否与 TOM 改变有关。
在 AD 中，将 TOM 亚基与 OXPHOS 复合物蛋白相关联。
从 AD 和年龄匹配的对照者的死后大脑新皮质（BA40）中提取富含线粒体的匀浆，用于通过免疫印迹法测量 Tom20、Tom22、Tom40 和 Tom70 以及 OXPHOS 复合物 I-V 的成分。
AD 中 Tom20 和 Tom70 的免疫反应性显著降低，OXPHOS 复合物 I 和 III 的成分也降低。Tom20 和 Tom70 与复合物 III 和 V 呈正相关，而 Tom20 也与复合物 IV 呈正相关。
某些 TOM 亚基的减少及其与特定 OXPHOS 复合物蛋白的相关性表明，受损的线粒体运输系统可能导致 AD 中先前观察到的氧化磷酸化缺陷。需要进一步的研究来证实本研究的相关性。
