Differential role of Presenilin-1 and -2 on mitochondrial membrane potential and oxygen consumption in mouse embryonic fibroblasts
| Autor: | Birgitta Wiehager, Bengt Winblad, Hernan Concha, Richard F. Cowburn, Maria Ankarcrona, Kjell Hultenby, Homira Behbahani, Jan Nedergaard, Irina G. Shabalina, Natasa Petrovic |
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| Rok vydání: | 2006 |
| Předmět: |
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Carbonyl Cyanide m-Chlorophenyl Hydrazone Population Biology Mitochondrion Mitochondrial apoptosis-induced channel Presenilin Membrane Potentials Cellular and Molecular Neuroscience Mice Adenosine Triphosphate Oxygen Consumption Presenilin-2 Presenilin-1 Animals Drug Interactions Enzyme Inhibitors skin and connective tissue diseases education Cells Cultured Membrane potential Mice Knockout education.field_of_study Analysis of Variance Dose-Response Relationship Drug Ionophores Membrane Proteins Carbocyanines Fibroblasts Embryo Mammalian Flow Cytometry Embryonic stem cell Cell biology Cell culture Apoptosis Mitochondrial Membranes Benzimidazoles Oligomycins |
| Zdroj: | Journal of neuroscience research. 84(4) |
| ISSN: | 0360-4012 |
| Popis: | Increasing evidence indicates that mitochondrial alterations contribute to the neuronal death in Alzheimer's disease (AD). Presenilin 1 (PS1) and Presenilin 2 (PS2) mutations have been shown to sensitize cells to apoptosis by mechanisms suggested to involve impaired mitochondrial function. We have previously detected active gamma-secretase complexes in mitochondria. We investigated the impact of PS/gamma-secretase on mitochondrial function using mouse embryonal fibroblasts derived from wild-type, PS1-/-, PS2-/- and PS double knock-out (PSKO) embryos. Measurements of mitochondrial membrane potential (DeltaPsim) showed a higher percentage of fully functional mitochondria in PS1-/- and PSwt as compared to PS2-/- and PSKO cells. This result was evident both in whole cell preparations and in isolated mitochondria. Interestingly, pre-treatment of isolated mitochondria with the gamma-secretase inhibitor L-685,458 resulted in a decreased population of mitochondria with high DeltaPsim in PSwt and PS1-/- cells, indicating that PS2/gamma-secretase activity can modify DeltaPsim. PS2-/- cells showed a significantly lower basal respiratory rate as compared to other cell lines. However, all cell lines demonstrated competent bioenergetic function. These data point toward a specific role of PS2/gamma-secretase activity for proper mitochondrial function and indicate interplay between PS1 and PS2 in mitochondrial functionality. |
| Databáze: | OpenAIRE |
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