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Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria
| Content Provider | Semantic Scholar |
|---|---|
| Author | Rapizzi, Elena Pinton, Paolo Szabadkai, György Wieckowski, Mariusz Roman Vandecasteele, Grégoire Baird, Geoff Tuft, Richard A. Fogarty, Kevin E. Rizzuto, Rosario |
| Copyright Year | 2002 |
| Abstract | Although the physiological relevance of mitochondrial Ca2+ homeostasis is widely accepted, no information is yet available on the molecular identity of the proteins involved in this process. Here we analyzed the role of the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane in the transmission of Ca2+ signals between the ER and mitochondria by measuring cytosolic and organelle [Ca2+] with targeted aequorins and Ca2+-sensitive GFPs. In HeLa cells and skeletal myotubes, the transient expression of VDAC enhanced the amplitude of the agonist-dependent increases in mitochondrial matrix Ca2+ concentration by allowing the fast diffusion of Ca2+ from ER release sites to the inner mitochondrial membrane. Indeed, high speed imaging of mitochondrial and cytosolic [Ca2+] changes showed that the delay between the rises occurring in the two compartments is significantly shorter in VDAC-overexpressing cells. As to the functional consequences, VDAC-overexpressing cells are more susceptible to ceramide-induced cell death, thus confirming that mitochondrial Ca2+ uptake plays a key role in the process of apoptosis. These results reveal a novel function for the widely expressed VDAC channel, identifying it as a molecular component of the routes for Ca2+ transport across the mitochondrial membranes. |
| Starting Page | 613 |
| Ending Page | 624 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 12438411v1 |
| Volume Number | 159 |
| Journal | The Journal of cell biology |
| Alternate Webpage(s) | http://jcb.rupress.org/content/jcb/159/4/613.full.pdf |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/4c/53/200205091.PMC2173108.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Aequorin Anatomical compartments Anions Apoptosis Calcium ion Cell Death Ceramides Mitochondrial Diseases Mitochondrial Membrane, Outer Mitochondrial Membranes Skeletal Myocytes VDAC1 wt Allele Voltage-Dependent Anion Channels voltage |
| Content Type | Text |
| Resource Type | Article |
