Min, Choon Kee Yeom, Dong Rim Lee, Kyung-Eun Kwon, Hye-Kyeong Kang, Moonkyung Kim, Yeon-Soo Park, Zee Yong Jeon, Hyesung Kim, Do Han 2024-01-20T13:32:59Z 2024-01-20T13:32:59Z 2021-09-05 2012-11-01 0264-6021 https://pubs.kist.re.kr/handle/201004/128662 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. English PORTLAND PRESS LTD CALCIUM SIGNAL TRANSMISSION ENDOPLASMIC-RETICULUM ER IDENTIFICATION INCREASES SKELETAL RELEASE CELLS Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is essential for Ca2+ transfer from the sarcoplasmic reticulum to the mitochondria in the heart Article 10.1042/BJ20120705 1 BIOCHEMICAL JOURNAL, v.447, pp.371 - 379 BIOCHEMICAL JOURNAL 447 371 379 scie scopus 000310489900005 2-s2.0-84867271703 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article CALCIUM SIGNAL TRANSMISSION ENDOPLASMIC-RETICULUM ER IDENTIFICATION INCREASES SKELETAL RELEASE CELLS cardiomyocyte high Ca2+ microdomain interorganelle Ca2+ transfer mitochondrial Ca2+ uptake ryanodine receptor (RyR) sarcoplasmic reticulum-mitochondria junction