Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction via OSCP in Alzheimer's disease.

ABSTRACT: Mitochondrial dysfunction is pivotal in inducing synaptic injury and neuronal stress in Alzheimer's disease (AD). Mitochondrial F1Fo ATP synthase deregulation is a hallmark mitochondrial defect leading to oxidative phosphorylation (OXPHOS) failure in this neurological disorder. Oligomycin sensitivity conferring protein (OSCP) is a crucial F1Fo ATP synthase subunit. Decreased OSCP levels and OSCP interaction with amyloid β (Aβ) constitute key aspects of F1Fo ATP synthase pathology in AD-related conditions. However, the detailed mechanisms promoting such AD-related OSCP changes have not been fully resolved. Here, we have found increased physical interaction of OSCP with Cyclophilin D (CypD) in AD cases as well as in an AD animal model (5xFAD mice). Genetic depletion of CypD mitigates OSCP lo

SUBMITTER: Gauba E 

PROVIDER: S-EPMC6250052 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature