title: Amyloid precursor protein, heat-shock proteins, and Bcl-2 form a complex in mitochondria and modulate mitochondria function and apoptosis in N2a cells.
abstract: Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis.
authors.affiliation: China Medical University, Taichung, Taiwan. tingting@mail.cmu.edu.tw
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Yang
authors.forename: Chao-Tien
authors.initials: CT
authors.lastname: Hsu
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D016895:Culture Media, Serum-Free; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2