valinomycin and Alzheimer-Disease

The aggregation of β-amyloid (Aβ) peptide in Alzheimer's disease (AD) is characterized by mitochondrial dysfunction and mitophagy impairment. Mitophagy is a homeostatic mechanism by which autophagy selectively eliminates damaged mitochondria. Valinomycin is a respiratory chain inhibitor that activates mitophagy via the PINK1/Parkin signaling pathway. However, the mechanism underlying the association between mitophagy and valinomycin in Aβ formation has not been explored. Here, we demonstrate that genetically modified (N2a/APP695swe) cells overexpressing a mutant amyloid precursor protein (APP) serve as an in vitro model of AD for studying mitophagy and ATP-related metabolomics. Our results prove that valinomycin induced a time-dependent increase in the mitophagy activation of N2a/APP695swe cells as indicated by increased levels of PINK1, Parkin, and LC3II as well as increased the colocalization of Parkin-Tom20 and fewer mitochondria (indicated by decreased Tom20 levels). Valinomycin significantly decreased Aβ

Topics: Adenosine Triphosphate; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cell Line, Tumor; Gene Expression Regulation; Humans; Ionophores; Membrane Potential, Mitochondrial; Membrane Transport Proteins; Metabolomics; Mice; Microtubule-Associated Proteins; Mitochondria; Mitochondrial Precursor Protein Import Complex Proteins; Mitophagy; Models, Biological; Neurons; Peptide Fragments; Protein Kinases; Receptors, Cell Surface; Ubiquitin-Protein Ligases; Valinomycin