Send to

Choose Destination
Nat Commun. 2016 May 6;7:11483. doi: 10.1038/ncomms11483.

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

Author information

Department of Biological Sciences, The University of Texas at Dallas, 800W. Campbell Road, Richardson, Texas 75080, USA.
School of Behavioral and Brain Sciences, The University of Texas at Dallas, 800W. Campbell Road, Richardson, Texas 75080, USA.
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, China.
Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Richardson, Texas 75390, USA.


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 (Aβ) 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 Aβ disrupt F1FO-ATP synthase, leading to reduced ATP production, elevated oxidative stress and activated mPT. The restoration of OSCP ameliorates Aβ-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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center