BCL-XL directly retrotranslocates the monomeric BAK
| Autor: | Zihao Mai, Fangfang Yang, Bin Wang, Tongsheng Chen, Yunyun Ma, Xiaoping Wang, Lu Wang, Mengyan Du |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
bcl-X Protein Bcl-xL Apoptosis Mitochondrion Transfection Time-Lapse Imaging Polymerization Cytosol Fluorescence Resonance Energy Transfer Humans Fluorescence loss in photobleaching biology Chemistry Optical Imaging Cell Biology Mitochondria Protein Transport Förster resonance energy transfer bcl-2 Homologous Antagonist-Killer Protein Flip biology.protein Biophysics biological phenomena cell phenomena and immunity HeLa Cells |
| Zdroj: | Cellular signalling. 61 |
| ISSN: | 1873-3913 |
| Popis: | BCL-XL, an anti-apoptotic BCL-2 family protein, potently inhibits BAK oligomerization and the formation of toxic mitochondrial pores in response to cellular stress. This report aims to explore which form of mitochondrial monomeric and oligomerized BAK can be retrotranslocated by BCL-XL. Fluorescence imaging of living cells co-expressing CFP-BCL-XL and YFP-BAK showed that BCL-XL markedly inhibited mitochondrial BAK oligomerization and resulted in partial cytosolic BAK distribution. Live-cell fluorescence resonance energy transfer (FRET) analyses showed that BAK auto-oligomerized on mitochondria and BCL-XL physically sequestrated monomeric BAK to prevent BAK oligomerization. Fluorescence loss in photobleaching (FLIP) analyses showed that BCL-XL retrotranslocated the monomeric BAK from mitochondria into cytosol, whereas monomeric BAK reduced the retrotranslocation rate of BCL-XL. Live-cell time-lapse imaging and FLIP experiments in living cells with BAK oligomers displayed that BCL-XL did not depolymerize or retrotranslocate the oligomerized BAK. Collectively, BCL-XL retrotranslocates monomeric instead of oligomerized BAK from mitochondria into cytosol. |
| Databáze: | OpenAIRE |
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