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

Author

Listed:
  • Simon J. Beck

    (The University of Texas at Dallas)

  • Lan Guo

    (The University of Texas at Dallas)

  • Aarron Phensy

    (School of Behavioral and Brain Sciences, The University of Texas at Dallas)

  • Jing Tian

    (The University of Texas at Dallas)

  • Lu Wang

    (The University of Texas at Dallas
    Shandong Provincial Hospital Affiliated to Shandong University)

  • Neha Tandon

    (The University of Texas at Dallas)

  • Esha Gauba

    (The University of Texas at Dallas)

  • Lin Lu

    (The University of Texas at Dallas
    Shandong Provincial Hospital Affiliated to Shandong University)

  • Juan M. Pascual

    (The University of Texas Southwestern Medical Center)

  • Sven Kroener

    (School of Behavioral and Brain Sciences, The University of Texas at Dallas)

  • Heng Du

    (The University of Texas at Dallas
    Shandong Provincial Hospital Affiliated to Shandong University)

Abstract

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.

Suggested Citation

  • Simon J. Beck & Lan Guo & Aarron Phensy & Jing Tian & Lu Wang & Neha Tandon & Esha Gauba & Lin Lu & Juan M. Pascual & Sven Kroener & Heng Du, 2016. "Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer’s disease," Nature Communications, Nature, vol. 7(1), pages 1-16, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11483
    DOI: 10.1038/ncomms11483
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