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Quasi‐synaptic calcium signal transmission between endoplasmic reticulum and mitochondria
Author(s) -
Csordás György,
Thomas Andrew P.,
Hajnóczky György
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.1.96
Subject(s) - endoplasmic reticulum , biology , mitochondrion , microbiology and biotechnology , calcium , calcium signaling , transmission (telecommunications) , signal (programming language) , biophysics , signal transduction , medicine , telecommunications , computer science , programming language
Transmission of cytosolic [Ca 2+ ] ([Ca 2+ ] c ) oscillations into the mitochondrial matrix is thought to be supported by local calcium control between IP 3 receptor Ca 2+ channels (IP3R) and mitochondria, but study of the coupling mechanisms has been difficult. We established a permeabilized cell model in which the Ca 2+ coupling between endoplasmic reticulum (ER) and mitochondria is retained, and mitochondrial [Ca 2+ ] ([Ca 2+ ] m ) can be monitored by fluorescence imaging. We demonstrate that maximal activation of mitochondrial Ca 2+ uptake is evoked by IP 3 ‐induced perimitochondrial [Ca 2+ ] elevations, which appear to reach values >20‐fold higher than the global increases of [Ca 2+ ] c . Incremental doses of IP 3 elicited [Ca 2+ ] m elevations that followed the quantal pattern of Ca 2+ mobilization, even at the level of individual mitochondria. In contrast, gradual increases of IP 3 evoked relatively small [Ca 2+ ] m responses despite eliciting similar [Ca 2+ ] c increases. We conclude that each mitochondrial Ca 2+ uptake site faces multiple IP3R, a concurrent activation of which is required for optimal activation of mitochondrial Ca 2+ uptake. This architecture explains why calcium oscillations evoked by synchronized periodic activation of IP3R are particularly effective in establishing dynamic control over mitochondrial metabolism. Furthermore, our data reveal fundamental functional similarities between ER–mitochondrial Ca 2+ coupling and synaptic transmission.