| Autor: |
Choon Kee, Min, Dong Rim, Yeom, Kyung-Eun, Lee, Hye-Kyeong, Kwon, Moonkyung, Kang, Yeon-Soo, Kim, Zee Yong, Park, Hyesung, Jeon, Do Han, Kim |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
The Biochemical journal. 447(3) |
| ISSN: |
1470-8728 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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