Loading...
Please wait, while we are loading the content...
Similar Documents
A modified calcium retention capacity assay clarifies the roles of extra- and intracellular calcium pools in mitochondrial permeability transition pore opening
| Content Provider | Scilit |
|---|---|
| Author | Harisseh, Rania Abrial, Maryline Chiari, Pascal Al-Mawla, Ribal Villedieu, Camille Tessier, Nolwenn Bidaux, Gabriel Ovize, Michel Gharib, Abdallah |
| Copyright Year | 2019 |
| Description | Journal: Journal of Biological Chemistry Calcium homeostasis is essential for cell survival and is precisely controlled by several cellular actors such as the sarco/endoplasmic reticulum and mitochondria. Upon stress induction, $Ca^{2+}$ released from sarco/endoplasmic reticulum stores and from extracellular $Ca^{2+}$ pools accumulates in the cytosol and in the mitochondria. This induces $Ca^{2+}$ overload and ultimately the opening of the mitochondrial permeability transition pore (mPTP), promoting cell death. Currently, it is unclear whether intracellular $Ca^{2+}$ stores are sufficient to promote the mPTP opening. $Ca^{2+}$ retention capacity (CRC) corresponds to the maximal $Ca^{2+}$ uptake by the mitochondria before mPTP opening. In this study, using permeabilized cardiomyocytes isolated from adult mice, we modified the standard CRC assay by specifically inducing reticular $Ca^{2+}$ release to investigate the respective contributions of reticular $Ca^{2+}$ and extracellular $Ca^{2+}$ to mPTP opening in normoxic conditions or after anoxia–reoxygenation. Our experiments revealed that $Ca^{2+}$ released from the sarco/endoplasmic reticulum is not sufficient to trigger mPTP opening and corresponds to ∼50% of the total $Ca^{2+}$ levels required to open the mPTP. We also studied mPTP opening after anoxia–reoxygenation in the presence or absence of extracellular $Ca^{2+}$. In both conditions, $Ca^{2+}$ leakage from internal stores could not trigger mPTP opening by itself but significantly decreased the CRC. Our findings highlight how a modified CRC assay enables the investigation of the role of reticular and extracellular $Ca^{2+}$ pools in the regulation of the mPTP. We propose that this method may be useful for screening molecules of interest implicated in mPTP regulation. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802505/pdf http://www.jbc.org/content/294/42/15282.full.pdf |
| Ending Page | 15292 |
| Page Count | 11 |
| Starting Page | 15282 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.ra119.009477 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 42 |
| Volume Number | 294 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-10-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Anoxia–reoxygenation Cardiac Infarction Mitochondrial Permeability Transition (mpt) Ryanodine Receptor Sarcoplasmic Reticulum (sr) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
