| First Author | Min CK | Year | 2012 |
| Journal | Biochem J | Volume | 447 |
| Issue | 3 | Pages | 371-9 |
| PubMed ID | 22867515 | Mgi Jnum | J:191292 |
| Mgi Id | MGI:5461415 | Doi | 10.1042/BJ20120705 |
| Citation | Min CK, et al. (2012) Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is essential for Ca(2)+ transfer from the sarcoplasmic reticulum to the mitochondria in the heart. Biochem J 447(3):371-9 |
| abstractText | The structural proximity and functional coupling between the SR (sarcoplasmic reticulum) and mitochondria have been suggested to occur in the heart. However, the molecular architecture involved in the SR-mitochondrial coupling remains unclear. In the present study, we performed various genetic and Ca2+-probing studies to resolve the proteins involved in the coupling process. By using the bacterial 2-hybrid, glutathione transferase pull-down, co-immunoprecipitation and immunocytochemistry assays, we found that RyR2 (ryanodine receptor type 2), which is physically associated with VDAC2 (voltage-dependent anion channel 2), was co-localized in SR-mitochondrial junctions. Furthermore, a fractionation study revealed that VDAC2 was co-localized with RyR2 only in the subsarcolemmal region. VDAC2 knockdown by targeted short hairpin RNA led to an increased diastolic [Ca2+] (calcium concentration) and abolishment of mitochondrial Ca2+ uptake. Collectively, the present study suggests that the coupling of VDAC2 with RyR2 is essential for Ca2+ transfer from the SR to mitochondria in the heart. |
