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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hoth, M. Button, D. C. Lewis, R. S. |
| Description | Author Affiliation: Hoth M ( Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5426, USA.); |
| Abstract | In addition to their well-known functions in cellular energy transduction, mitochondria play an important role in modulating the amplitude and time course of intracellular Ca(2+) signals. In many cells, mitochondria act as Ca(2+) buffers by taking up and releasing Ca(2+), but this simple buffering action by itself often cannot explain the organelle's effects on Ca(2+) signaling dynamics. Here we describe the functional interaction of mitochondria with store-operated Ca(2+) channels in T lymphocytes as a mechanism of mitochondrial Ca(2+) signaling. In Jurkat T cells with functional mitochondria, prolonged depletion of Ca(2+) stores causes sustained activation of the store-operated Ca(2+) current, I(CRAC) (CRAC, Ca(2+) release-activated Ca(2+)). Inhibition of mitochondrial Ca(2+) uptake by compounds that dissipate the intramitochondrial potential unmasks Ca(2+)-dependent inactivation of I(CRAC). Thus, functional mitochondria are required to maintain CRAC-channel activity, most likely by preventing local Ca(2+) accumulation near sites that govern channel inactivation. In cells stimulated through the T-cell antigen receptor, acute blockade of mitochondrial Ca(2+) uptake inhibits the nuclear translocation of the transcription factor NFAT in parallel with CRAC channel activity and [Ca(2+)](i) elevation, indicating a functional link between mitochondrial regulation of I(CRAC) and T-cell activation. These results demonstrate a role for mitochondria in controlling Ca(2+) channel activity and signal transmission from the plasma membrane to the nucleus. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 97 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2000-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium Channels Physiology Ion Channel Gating Mitochondria Signal Transduction T-Lymphocytes Metabolism Transcriptional Activation Jurkat Cells Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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