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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Palmer, Amy E. Gorski, Jessica A. Dittmer, Philip J. Miranda, Jose G. |
| Description | Author Affiliation: Dittmer PJ ( Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.) |
| Abstract | Transition metals are essential enzyme cofactors that are required for a wide range of cellular processes. Paradoxically, whereas metal ions are essential for numerous cellular processes, they are also toxic. Therefore cells must tightly regulate metal accumulation, transport, distribution, and export. Improved tools to interrogate metal ion availability and spatial distribution within living cells would greatly advance our understanding of cellular metal homeostasis. In this work, we present genetically encoded sensors for Zn2+ based on the principle of fluorescence resonance energy transfer. We also develop methodology to calibrate the probes within the cellular environment. To identify both sources of and sinks for Zn2+, these sensors are genetically targeted to specific locations within the cell, including cytosol, plasma membrane, and mitochondria. Localized probes reveal that mitochondria contain an elevated pool of Zn2+ under resting conditions that can be released into the cytosol upon glutamate stimulation of hippocampal neurons. We also observed that Zn2+ is taken up into mitochondria following glutamate/Zn2+ treatment and that there is heterogeneity in both the magnitude and kinetics of the response. Our results suggest that mitochondria serve as a source of and a sink for Zn2+ signals under different cellular conditions. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 24 |
| Volume Number | 284 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2009-06-12 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Fluorescence Resonance Energy Transfer Fluorescent Dyes Pharmacokinetics Mitochondria Metabolism Neurons Zinc Animals Calibration Cell Membrane Cytosol Glutamic Acid Pharmacology HeLa Cells Hippocampus Cytology Homeostasis Physiology Rats, Sprague-Dawley Transfection Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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