VDACs: An Outlook on Biochemical Regulation and Function in Animal and Plant Systems

Abstract

The voltage-dependent anion channels (VDACs) are the most abundant proteins present on the outer mitochondrial membrane. They serve a myriad of functions ranging from energy and metabolite exchange to highly debatable roles in apoptosis. Their role in molecular transport puts them on the center stage as communicators between cytoplasmic and mitochondrial signaling events. Beyond their general role as interchangeable pores, members of this family may exhibit specific functions. Even after nearly five decades of their discovery, their role in plant systems is still a new and rapidly emerging field. The information on biochemical regulation of VDACs is limited. Various interacting proteins and post-translational modifications (PTMs) modulate VDAC functions, amongst these, phosphorylation is quite noticeable. In this review, we have tried to give a glimpse of the recent advancements in the biochemical/interactional regulation of plant VDACs. We also cover a critical analysis on the importance of PTMs in the functional regulation of VDACs. Besides, the review also encompasses numerous studies which can identify VDACs as a connecting link between Ca²⁺ and reactive oxygen species signaling in special reference to the plant systems.

Keywords: CBL–CIPK; Ca2+; biochemical regulation; cell signaling; cellular homeostasis; mitochondrial channel; phosphorylation; reactive oxygen species.

FIGURE 1

Voltage-dependent anion channels in plants. The biochemical action and interaction of VDACs in plants affects their functional behavior. This image depicts the regulation and interaction of VDACs with binding proteins and chemical compounds. CBL1, Calcineurin B-like protein; TRXm2, chloroplast protein thioredoxin m2; MT2b, metallothionein 2b; H₂O₂, hydrogen peroxide; KP1, plant kinesin protein 1; PR10.1, pathogenesis-related 10.1; C₁₃H₁₆O₃, precocene II; C₂₁H₂₀O₆, curcumin; C₂₁H₃₀O₂, cannabidiol.

FIGURE 2

Representation of functional implications of VDACs, Ca²⁺, and ROS in cellular signaling. This hypothetical model traces pathways through which VDAC may regulate Ca²⁺ and ROS signaling in plants. We discuss here four possible routes that we currently posit are VDAC mediated connection between Ca²⁺ and ROS signaling. (1) When cytosolic Ca²⁺ level increases on perception of stimuli (generation of Ca²⁺ signature), these signals are transduced downstream, where they influence the activity of VDACs. This might results in increased level of ROS in mitochondria. (2) VDAC serves passively to regulate Ca²⁺ levels in mitochondria. (3) Stimuli such as oxidative stress (inclusive of increased ROS level) and touch response results in generation of Ca²⁺ signature in mitochondria, independent of cytosolic Ca²⁺ signature. (4) VDAC can be a candidate protein that leads to flux of Ca²⁺/ROS from inter-membrane space to cytosol. Further, VDACs are known to connect ER based Ca²⁺ signaling and mitochondria through Ca²⁺ and ROS molecules and this may depict another possible mechanism of how VDAC connects Ca²⁺ and ROS. These hypothetical routes may (or may not) be connected. ER, endoplasmic reticulum; ROS, reactive oxygen species; grp75, glucose related protein 75; Ca²⁺, calcium; VDAC, voltage-dependent anion channel.