Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer's disease

作者

Beck, SJ;Guo, L;Phensy, A;Tian, J;Wang, L;Tandon, N;Gauba, E;Lu, L;Pascual, JM;Kroener, S;Du, H

作者单位

[Beck, Simon J.; Guo, Lan; Tian, Jing; Wang, Lu; Tandon, Neha; Gauba, Esha; Lu, Lin; Du, Heng] Univ Texas Dallas, Dept Biol Sci, 800W Campbell Rd, Richardson, TX 75080 USA.;-;[Phensy, Aarron; Kroener, Sven] Univ Texas Dallas, Sch Behav & Brain Sci, 800W Campbell Rd, Richardson, TX 75080 USA.;-;[Wang, Lu; Lu, Lin; Du, Heng] Shandong Univ, Dept Neurol, Shandong Prov Hosp, 324 Jingwu Weiqi Rd, Jinan 250021, Shandong, Peoples R China.;-;[Pascual, Juan M.] Univ Texas Southwestern Med Ctr, Dept Neurol & Neurotherapeut, 5323 Harry Hines Blvd, Richardson, TX 75390 USA.

摘要

F1FO-ATP synthase is critical for mitochondrial functions. The deregulation of this enzyme results in dampened mitochondrial oxidative phosphorylation (OXPHOS) and activated mitochondrial permeability transition (mPT), defects which accompany Alzheimer's disease (AD). However, the molecular mechanisms that connect F1FO-ATP synthase dysfunction and AD remain unclear. Here, we observe selective loss of the oligomycin sensitivity conferring protein (OSCP) subunit of the F1FO-ATP synthase and the physical interaction of OSCP with amyloid beta (A beta) in the brains of AD individuals and in an AD mouse model. Changes in OSCP levels are more pronounced in neuronal mitochondria. OSCP loss and its interplay with A beta disrupt F1FO-ATP synthase, leading to reduced ATP production, elevated oxidative stress and activated mPT. The restoration of OSCP ameliorates A beta-mediated mouse and human neuronal mitochondrial impairments and the resultant synaptic injury. Therefore, mitochondrial F1FO-ATP synthase dysfunction associated with AD progression could potentially be prevented by OSCP stabilization.

关键词

CYTOCHROME-C-OXIDASE; PERMEABILITY TRANSITION PORE; SENSITIVITY CONFERRING PROTEIN; F1F0 ATP SYNTHASE; AMYLOID-BETA; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; MOUSE MODEL; A-BETA; ENTORHINAL CORTEX

基本信息

所属机构:

归属医师: 卢林

PMID：27151236

UT：000375494500001

刊名:NATURE COMMUNICATIONS

年，卷(期):2016年7卷

DOI：10.1038/ncomms11483

附件： pdf

收录: SCIE