Figure 4.

mPTP opening corresponds to a bistable switch. Numerical bifurcation diagrams of the fraction of open mPTP, $PTP$ (A) and $\mathrm{\Delta }\mathrm{\Psi }$ (B) as a function of added Ca${}^{2+}$. Blue and red curves stand for trajectories following Ca${}^{2+}$ additions (from left to right) or Ca${}^{2+}$ removal (from right to left), respectively. The equivalent bifurcation diagrams of $C_m$ and $C_{em}$ as a function of added Ca${}^{2+}$ are shown in Fig. S1. (C,D) Experimental evidence for bistability of the mPTP in a hepatocyte mitochondrial suspension. Ca${}^{2+}$ is monitored in the medium with 5 $\mu$$M$ Fluo-4 (C,D) and $\mathrm{\Delta }\mathrm{\Psi }$ with 5 $\mu$$M$ TMRM (SI Appendix) (D). In both cases, the concentration of EGTA necessary to close the mPTP is larger than the concentration of Ca${}^{2+}$ that allowed its opening. This highlights the existence of hysteresis as schematised in the inset in Panel (C). Panels (C,D) are representative of 12 similar experiments.