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The C-terminal transmembrane domain of Bcl-xL mediates changes in mitochondrial morphology |
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| Authors: | Zheng Jing-Yi Tsai Yien-Che Kadimcherla Pradeep Zhang Rong Shi Julia Oyler George A Boustany Nada N |
| Affiliation: | * Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey † Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, Maryland ‡ Department of Computer and Information Science and Engineering, University of Florida, Gainesville, Florida § Department of Medicine, University of Maryland, Baltimore, Maryland ¶ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland |
| Abstract: | We investigate the effect of mitochondrial localization and the Bcl-xL C-terminal transmembrane (TM) domain on mitochondrial morphology and subcellular light scattering. CSM 14.1 cell lines stably expressed yellow fluorescent protein (YFP), YFP-Bcl-xL, YFP-Bcl-xL-ΔTM, containing the remainder of Bcl-xL after deletion of the last 21 amino acids corresponding to the TM domain, or YFP-TM, consisting of YFP fused at its C-terminal to the last 21 amino acids of Bcl-xL. YFP-Bcl-xL and YFP-TM localized to the mitochondria. Their expression decreased the intensity ratio of wide-to-narrow angle forward scatter by subcellular organelles, and correlated with an increase in the proportion of mitochondria with an expanded matrix having greatly reduced intracristal spaces as observed by electron microscopy. Cells expressing YFP-TM also exhibited significant autophagy. In contrast, YFP-Bcl-xL-ΔTM was diffusely distributed in the cells, and its expression did not alter light scattering or mitochondrial morphology compared with parental cells. Expression of YFP-Bcl-xL or YFP-Bcl-xL-ΔTM provided significant resistance to staurosporine-induced apoptosis. Surprisingly however, YFP-TM expression also conferred a moderate level of cell death resistance in response to staurosporine. Taken together, our results suggest the existence of a secondary Bcl-xL function that is mediated by the transmembrane domain, alters mitochondrial morphology, and is distinct from BH3 domain sequestration. |
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