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
- PMID: 22867515
- DOI: 10.1042/BJ20120705
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
Abstract
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.
Similar articles
-
VDAC2 as a novel target for heart failure: Ca2+ at the sarcomere, mitochondria and SR.Cell Calcium. 2022 Jun;104:102586. doi: 10.1016/j.ceca.2022.102586. Epub 2022 Mar 28. Cell Calcium. 2022. PMID: 35429733 Free PMC article. Review.
-
Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium.Cell Death Dis. 2014 Dec 18;5(12):e1573. doi: 10.1038/cddis.2014.526. Cell Death Dis. 2014. PMID: 25522267 Free PMC article.
-
Voltage-dependent anion channel 2 modulates resting Ca²+ sparks, but not action potential-induced Ca²+ signaling in cardiac myocytes.Cell Calcium. 2011 Feb;49(2):136-43. doi: 10.1016/j.ceca.2010.12.004. Epub 2011 Jan 15. Cell Calcium. 2011. PMID: 21241999
-
Sarcoplasmic reticulum calcium leak and cardiac arrhythmias.Biochem Soc Trans. 2007 Nov;35(Pt 5):952-6. doi: 10.1042/BST0350952. Biochem Soc Trans. 2007. PMID: 17956253 Review.
-
NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release.Circ Res. 2004 Mar 5;94(4):478-86. doi: 10.1161/01.RES.0000115554.65513.7C. Epub 2003 Dec 29. Circ Res. 2004. PMID: 14699012
Cited by
-
So close, yet so far away: the relationship between MAM and cardiac disease.Front Cardiovasc Med. 2024 Feb 5;11:1353533. doi: 10.3389/fcvm.2024.1353533. eCollection 2024. Front Cardiovasc Med. 2024. PMID: 38374992 Free PMC article. Review.
-
A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptake.Life Sci Alliance. 2023 Nov 27;7(2):e202302278. doi: 10.26508/lsa.202302278. Print 2024 Feb. Life Sci Alliance. 2023. PMID: 38012000 Free PMC article.
-
Transcriptomic Profiling of Tetrodotoxin-Induced Neurotoxicity in Human Cerebral Organoids.Mar Drugs. 2023 Nov 10;21(11):588. doi: 10.3390/md21110588. Mar Drugs. 2023. PMID: 37999412 Free PMC article.
-
Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies.Antioxidants (Basel). 2023 Feb 2;12(2):353. doi: 10.3390/antiox12020353. Antioxidants (Basel). 2023. PMID: 36829912 Free PMC article. Review.
-
E as in Enigma: The Mysterious Role of the Voltage-Dependent Anion Channel Glutamate E73.Int J Mol Sci. 2022 Dec 23;24(1):269. doi: 10.3390/ijms24010269. Int J Mol Sci. 2022. PMID: 36613710 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous