Ca2+ accumulation
Contributor: Saverio Marchi
{"name":"Ca2+ accumulation","theorem":{"head":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":1},{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"CCDC109B","position":2},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"MCUR1","position":1},{"_type":"protein","name":"MCU","position":2}]},{"_type":"protein","name":"SMDT1","position":2},{"_type":"protein","name":"MICU1","position":4},{"_type":"protein","name":"MICU2","position":4}]}]},"body":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":16},{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"CCDC109B","position":2},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"MCUR1","position":1},{"_type":"protein","name":"MCU","position":2}]},{"_type":"protein","name":"SMDT1","position":2},{"_type":"protein","name":"MICU1","position":4},{"_type":"protein","name":"MICU2","position":4}]}]}},"steps":[{"head":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":16},{"_type":"interaction","position":8,"components":[{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8}]}]},"body":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":16},{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8}]}},{"head":{"_type":"interaction","position":8,"components":[{"_type":"molecule","name":"Ca2+","position":16},{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8}]},"body":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":16},{"_type":"interaction","position":8,"components":[{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8}]}]}},{"head":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":4},{"_type":"interaction","position":8,"components":[{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8}]}]},"body":{"_type":"interaction","position":8,"components":[{"_type":"molecule","name":"Ca2+","position":16},{"_type":"protein","name":"VDAC1","position":8},{"_type":"protein","name":"VDAC2","position":8},{"_type":"protein","name":"VDAC3","position":8}]}},{"head":{"_type":"interaction","position":0,"components":[{"_type":"molecule","name":"Ca2+","position":4},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"CCDC109B","position":2},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"MCUR1","position":1},{"_type":"protein","name":"MCU","position":2}]},{"_type":"protein","name":"SMDT1","position":2},{"_type":"protein","name":"MICU1","position":4},{"_type":"protein","name":"MICU2","position":4}]}]},"body":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":4},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"CCDC109B","position":2},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"MCUR1","position":1},{"_type":"protein","name":"MCU","position":2}]},{"_type":"protein","name":"SMDT1","position":2},{"_type":"protein","name":"MICU1","position":4},{"_type":"protein","name":"MICU2","position":4}]}]}},{"head":{"_type":"conjunction","components":[{"_type":"molecule","name":"Ca2+","position":1},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"CCDC109B","position":2},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"MCUR1","position":1},{"_type":"protein","name":"MCU","position":2}]},{"_type":"protein","name":"SMDT1","position":2},{"_type":"protein","name":"MICU1","position":4},{"_type":"protein","name":"MICU2","position":4}]}]},"body":{"_type":"interaction","position":0,"components":[{"_type":"molecule","name":"Ca2+","position":4},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"CCDC109B","position":2},{"_type":"interaction","position":2,"components":[{"_type":"protein","name":"MCUR1","position":1},{"_type":"protein","name":"MCU","position":2}]},{"_type":"protein","name":"SMDT1","position":2},{"_type":"protein","name":"MICU1","position":4},{"_type":"protein","name":"MICU2","position":4}]}]}}]}
Theorem
Information
Cytosolic Ca2+ bypasses the outer mitochondrial membrane through Voltage-Dependent Anion (VDAC) channels and accumulates inside the matrix through the Uniporter complex (Uniplex).
References:
Pathak T, Trebak M. Mitochondrial Ca2+ signaling. Pharmacol Ther. 2018 Dec;192:112-123. doi: 10.1016/j.pharmthera.2018.07.001. Epub 2018 Jul 20. PMID: 30036491.
Giorgi C, Marchi S, Pinton P. The machineries, regulation and cellular functions of mitochondrial calcium. Nat Rev Mol Cell Biol. 2018
Nov;19(11):713-730. doi: 10.1038/s41580-018-0052-8. Erratum in: Nat Rev Mol Cell Biol. 2018 Sep 24;: PMID: 30143745.
Williams GS, Boyman L, Chikando AC, Khairallah RJ, Lederer WJ. Mitochondrial calcium uptake. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10479-86. doi: 10.1073/pnas.1300410110. Epub 2013 Jun 12. PMID: 23759742.
Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012 Sep;13(9):566-78. doi: 10.1038/nrm3412. Epub 2012 Aug 1. PMID: 22850819.
Link to other Databases:
Reactome: https://reactome.org/PathwayBrowser/#/R-HSA-8949215&PATH=R-HSA-382551
Mitochondrial processes
Demonstrative and biological steps
Dynamic view
Mito-location
Not Available/Not Relevant
Matrix
Inner Membrane
Inter-Membrane Space
Outer Membrane
