A major player in necrosis is the mitochondrial permeability transition pore, a non-specific pore that opens in the inner mitochondrial membrane promoting massive swelling of mitochondria, drop of membrane potential, rupture of the outer membrane and cell death (Halestrap et al., 2002; Baines et al., 2005; Bernardi et al., 2006; Du and Yan, 2010).
The MPTP opening leads to the loss of mitochondrial membrane potential, mitochondrial swelling, rupture of the outer mitochondrial membrane and the release of cytochrome c.
The MPTP opening leads to loss of mitochondrial membrane potential, mitochondrial swelling, rupture of the outer mitochondrial membrane and release of cytochrome c.
While transient PTP opening may serve the purpose of providing a fast calcium release mechanism, persistent PTP opening is followed by deregulated release of matrix calcium, loss of mitochondrial membrane potential, mitochondrial swelling and rupture of the OMM.
In contrast, during forms of cellular necrosis, one key regulated event is the opening of the mitochondrial permeability transition pore (MPTP), a protein complex that was proposed to span the inner and outer mitochondrial membranes in facilitating loss of the inner membrane potential, swelling, and eventual rupture of the organelle (Halestrap, 2009; Tait and Green, 2010).
This may explain the cell in Figure 5b, which exhibited a sudden loss of mitochondrial membrane potential in parallel with canalicular membrane rupture.
The resting membrane potential (Vrest) was estimated immediately following membrane patch rupture in current clamp mode with zero holding current (I = 0) and, like all voltages in this paper, was adjusted for an estimated liquid junction potential of ∼+15 mV.
The RMP (resting membrane potential) was measured 5 min after the seal was ruptured.
As for pneumococci, Ruthenium Red inhibited depolarization and death, with membrane potential being reduced by 52.8% (P<0.01; Fig. 8B), membrane rupture by 72.1% (P<0.01; Fig. 8C) and log10 death decreased by 62.4% (P<0.05; Fig. 8D).
Resting membrane potential was directly measured in current-clamp mode after membrane rupture and only cells with a resting membrane potential more negative than −50 mV were studied.
Necrosis, on the other hand, is less well-characterized and associated with features including rupture of cell plasma membrane, loss of mitochondria membrane potential (MMP), depletion of adenosine triphosphate (ATP) levels and overproduction of ROS.
