Table 3.
Proposed PTP and PTP regulatory molecules
| Protein/complex (Abbreviation, gene) | Evidence for role in PTP | Probable role in the PTP | |
| For | Against | ||
| Adenine nucleotide translocase (ANT, Slc25a4-6) | PTP-like activity of ANT in bilayers (Ruck et al. 1998), effect of ADP. ATP, ATR and bongkrekic acid on PTP activity (Haworth and Hunter 1979; Hunter and Haworth 1979a, b) | Deletion of ANTI and ANT2 (Slc25a4 and Slc25a5) does not eliminate PTP activity, but decreases its sensitivity to Ca2+ (Kokoszka et al. 2004) | Regulates PTP activity, perhaps through interactions with ATP synthase as part of the synthasome |
| ATP synthase | Binds to or associates with PTP regulatory molecules (ANT, CypD, mtCK. PiC; see text). PTP activity found in ATP synthase dimers and the C-subunit ring (Alavian et al. 2011; Giorgio et al. 2013) | The exact mechanisms of PTP regulation within ATP synthase remain unknown | Although ATP synthase dimers have been proposed to create the pore of the PTP. more evidence exists suggesting that the F0 C-ring does this, but how this is regulated remains unresolved |
| Creatine kinase, mitochondrial (mtCK, Cknit1A, 1B. 2) | Knockout of Ckmtl increases susceptibility to PTP (Datler et al. 2014) | Regulatory, connects energy-producing and energy- consuming mechanism (Saks et al. 2012) | |
| Cyclophilin D (CypD, Ppif) | Inhibition of CypD with CsA closes the PTP | Deletion of CypD does not eliminate PTP (Baines et al. 2005; Basso et al. 2005; Nakagawa et al. 2005; Schinzel et al. 2005) | Regulatory, binds to ATP synthase at OSCP but exact mechanism unknown |
| Hexokinase (Hk1-4) | Phosphorylation of glucose by mitochondrial bound HK 1 and 11 inhibits PTP (Azoulay-Zohar et al. 2004) | Regulatory, binds to VDAC, creates micro-compartments with high capacitive coupling to favor ADP/ATP exchange (Vyssokikh and Brdiczka 2003) | |
| Phosphate carrier (PiC, Slc25a3) | Binds to ANT and CypD (Leung et al. 2008) | Deletion of PiC does not eliminate PTP activity, but decreases its sensitivity to Ca2+ (Gutierrez-Aguilar et al. 2014: Kwong et al. 2014) | Regulates PTP activity, perhaps through interactions with ATP synthase as part of the synthasome |
| Polyphosphate and Polyhydro xybuty rate | The naturally occurring molecules increase PTP (Elustondo et al. 2013; Seidlmayer et al. 2012; Stotz et al. 2014) | Regulates PTP activity, perhaps through interactions with ATP synthase and the C-ring | |
| Spastic paraplegia 7 (Spg7) | Binds to CypD and VDAC. and its knockdown inhibits the PT (Shanmughapriya et al. 2015) | Regulates the PTP through currently unknown mechanisms. Its role in pore formation is unknown | |
| Translocator protein of 18 kDa (TSPO. Tspo) | TSPO was isolated with ANT and VDAC (McEnery etal. 1992) | Deletion of TSPO does not eliminate PTP activity (Sileikyte et al. 2014) | Probably plays no role in creating the PTP |
| Unfolded proteins | He and Lemasters (2002) | Unknown | |
| Voltage-dependent anion carrier (VDAC, Vdac 1-3) | Pathway for cytochrome c release (Shimizu et al. 2000) | Deletion of VDAC1, VDAC2, and VDAC3 does not eliminate PTP activity (Baines et al. 2007) | Interaction with HK or mtCK keeps VDAC in anion- selective state (Vyssokikh and Brdiczka 2003) |