1.B.8.1.1
Voltage-dependent anion channel-1 (VDAC1; OMP2; Por1) porin.  It is a component of the mitochondrial permeability transition pore (mPTP) which includes cyclophilin D, VDAC and the adenine nucleotide translocator (TC subfamily 2.A.29.1) (Austin et al. 2013). Mitochondrial synthesis of cardiolipin (CL) and phosphatidylethanolamine requires the transport of their precursors, phosphatidic acid and phosphatidylserine, respectively, to the mitochondrial inner membrane. The Ups1-Mdm35 and Ups2-Mdm35 complexes transfer phosphatidic acid and phosphatidylserine, respectively, between the mitochondrial outer and inner membranes. A Ups1-independent CL accumulation pathway requires several mitochondrial proteins with unknown functions including Mdm31. Miyata et al. 2018 identified VDAC1 (Por1) as a protein that interacts with both Mdm31 and Mdm35. Depletion of the porins Por1 and Por2 destabilized Ups1 and Ups2, decreased CL levels by ~90%, and caused loss of Ups2-dependent phosphatidylethanolamine synthesis, but did not affect Ups2-independent phosphatidylethanolamine synthesis in mitochondria. Por1 mutations that affected its interactions with Mdm31 and Mdm35, but not respiratory growth, also decreased CL levels. Using HeLa cells, the authors showed that mammalian porins also function in mitochondrial CL metabolism. Thus, yeast porins function in mitochondrial phospholipid metabolism, and porin-mediated regulation of CL metabolism appears to be evolutionarily conserved. VDACs are targeted to mitocondria via a C-terminal hydrophobic β-strand terminated by a hydrophiic residue (Klinger et al. 2019). Pentenediol-type compounds bind to VDAC1 (Unten et al. 2019). VDACs play a major role in the mitochondrial permeability transition, and inhibition of the MPT improves bone fracture repair (Shares et al. 2020). Gallic acid inhibits the celecoxib-induced mitochondrial permeability transition and reduces its toxicity (Salimi et al. 2021).