Plant VDAC Selectivity and Voltage-Dependence are Uncoupled

Abstract

The mitochondrial respiration requires the exchange of inorganic ions and metabolites between the cytoplasm and the mitochondrial matrix. This entails the translocation of these solutes through both inner and outer mitochondrial membranes. This function is fulfilled by the voltage-dependent anion-selective channel (VDAC) in the mitochondrial outer membrane. A typical feature of VDAC is its voltage-dependence. At low voltage, typically |V|<20mV, it is in its open state and it switches to subconductance states upon increasing the voltage amplitude. It is generally assumed that both selectivity and voltage-dependence of VDAC are coupled: the VDAC is anion selective in the open state but cation selective in subconducance states. However, it was shown that the selectivity of the open state can spontaneously switch between anion and cation selectivity [1]. The origin of this selectivity inversion is not known. We studied the selectivity of the plant PcVDAC32 that belong to the canonical isoform of VDAC including mammalian VDAC1 and yeast VDAC1 with which it shares similar electrophysiological properties as well as secondary structure content [2]. We show that change of selectivity occurs in open and in subconductance states without being related to gating. In the open state the probability of selectivity inversion is regulated by the membrane lipid composition, the ion strength and the magnitude of the ion gradient across the membrane. Furthermore no matter the experimental condition the selectivity inversion is not correlated to a change in channel conductance. Altogether these results indicate that there is no correlation between the VDAC selectivity and its voltage-dependence.[1] Pavlov, E. et al. (2005) BBA 1710: 96.[2] Homble, F., Krammer,E.V. and Prevost, M. (2012) BBA 1818: 1486.This work was supported by the FRS-FNRS (Belgium).