The permeability transition in heart mitochondria is regulated synergistically by ADP and cyclosporin A.

Dynamics of the permeability transition pore size in isolated mitochondria and mitoplasts

“…Therefore, the variability in the size of the PTP could be explained by both the occurrence of the pore in the sub‐maximum conductance state and a fast flickering, which interferes with the entrance of PEG. In agreement with this view, in several studies of the PTP induction by Ca 2+ /P i , the phase of PTP permeability to H + /Me preceded the phase of permeability to sucrose and mannitol 37‐40 . This was interpreted as direct evidence of the PTP transition from one conductance state to another and of the identity of the PTP and MMC.…”

“…Synchronous registration of the MIM permeability to H+/Me and larger solute molecules revealed the capability of PTP to transit from the unstable state of low‐conductance (permeability for H+/Me) to a stable high‐conductance state (permeability to sucrose, mannitol, and calcein) 30,39,40,48,49,55,56 . Here, by monitoring the PTP size by several sequential measurements in the same mitochondrial sample, we showed that, even in a high‐conductance state, the PTP tends to grow (Figure 2B‐E).…”

“…In agreement with this view, in several studies of the PTP induction by Ca 2+ /P i , the phase of PTP permeability to H + /Me preceded the phase of permeability to sucrose and mannitol. [37][38][39][40] This was interpreted as direct evidence of the PTP transition from one conductance state to another and of the identity of the PTP and MMC.…”

NAD(H) Regulates the Permeability Transition Pore in Mitochondria through an External Site

“…The release of Ca 2+ from mitochondria can occur much earlier than the complete opening of mPTP and entry into the matrix of low-molecular-weight solutes (K + , Cl − , sucrose, mannitol, etc. ), which cause the swelling of mitochondria [26][27][28][29]. The molecular weight of NAD(H) is significantly greater than the molecular weight of the hydrated forms of all the compounds mentioned above.…”

“…Since NAD(H) cannot penetrate through the intact inner mitochondrial membrane (IMM) [24,25], these data could indicate the existence of a NAD(H)-dependent site of mPTP regulation in the OMM or the intermembrane space (IMS) of mitochondria. However, it is well known that mPTP opening can be reversible [9,[26][27][28][29], while exogenous NADH can penetrate through the opened mPTP and interact with matrix enzymes [30]. According to the earlier data of Haworth and Hunter, it was exogenous NAD(H) that caused the closure of the opened mPTP by acting on the allosteric regulatory site in the matrix [8,9].…”