Figure 7

Schematic representation of how mitochondria modulate [Ca²⁺]_Cyt.

IP₃R channel is regulated by Ca²⁺ in a biphasic manner: a lower [Ca²⁺]_Cyt promotes Ca²⁺ release and causes its elevation whereas higher [Ca²⁺]_Cyt inhibits Ca²⁺ release. There is a critical distance at which 50% of the IP₃R-released Ca²⁺ ions are taken up by mitochondria. When r<r_crt, mitochondrial Ca²⁺ uptake exerts a negative control on IP₃R-released Ca²⁺ by preventing the positive effect of low [Ca²⁺]_Cyt on IP₃R; whilst when r > r_crt, mitochondrial Ca²⁺ uptake provides a positive modulation on IP₃R-released Ca²⁺ by suppressing the negative effect of high [Ca²⁺]_Cyt on IP₃R. Ca²⁺ oscillations merely occur for moderate values of [IP₃] (orange range) with physiological amplitude (gray range), so the optimal distance of IP₃R-MCU should be within the intersection zone between the gray and orange range.