**1. Introduction**

Transporters play important roles in the transport of nutrients, hormones, and metabolites for the purposes of growth, development, and adaptation to stresses. To deliver the substrates in a specific direction, active transporters, which can transport substrates against their concentration gradients, are required. Transmembrane transporters mediate the transport of substrates across biological membranes. The polypeptides of transmembrane transporters contain transmembrane segments (TMSs), which are integrated in the membrane [1]. The segments of the integral membrane proteins embedded in the membrane are called transmembrane domains (TMDs) [2]. Such active transport is often driven by the proton gradient across the cellular/subcellular membrane. Therefore, changes in the cellular/subcellular pH could regulate the transport activities and determine the direction of transport. In each subcellular compartment, the pH is highly regulated and ye<sup>t</sup> dynamic. It has been reported that stresses result in changes in cellular pH, which can form part of the stress signal [3]. For example, it was reported that flooding and drought stress induced an increase in the pH of xylem sap [3]; ionic stress induced an increase in cytosolic pH and a decrease in vacuolar pH [4]; fungal infection induced an increase in the pH of apoplastic sap; and pattern-triggered immunity (PTI) induced a decrease in cytosolic

**Citation:** Ku, Y.-S.; Cheng, S.-S.; Ng, M.-S.; Chung, G.; Lam, H.-M. The Tiny Companion Matters: The Important Role of Protons in Active Transports in Plants. *Int. J. Mol. Sci.* **2022**, *23*, 2824. https://doi.org/ 10.3390/ijms23052824

Academic Editor: Masoud Jelokhani-Niaraki

Received: 29 November 2021 Accepted: 2 March 2022 Published: 4 March 2022

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pH [5]. The changes in pH in different cellular compartments may imply the change in pH difference as well as the change in electrical potential difference across the biological membrane. Furthermore, the pH itself could also affect the activity of the transporter and the protonation state of the substrates to be transported. Altogether, these factors influence the transport efficiency and, thus, bring forth the physiological regulations.

In plants, cellular pH has been reported to be mainly regulated by proton pumps including the plasma membrane ATPase (PM-ATPase), the vacuolar-type ATPase (V-ATPase), the vacuolar pyrophosphatase (V-PPase) [6,7] and Na+/H+ antiporter (NHX) [8]. PM-ATPase hydrolyzes ATP to release H+, which is then exported out of the cell by PM-ATPase [9]. Such transport of H+ results in the proton gradient and electrical potential gradient across the membrane [9,10]. Under salt stress, it has been suggested that the PM-ATPase creates the electrochemical proton gradient to enable the extrusion of Na+ out of the cell or the intrusion of Na+ inside the vacuole by NHX [11]. V-ATPase has been known to be responsible for vacuolar acidification and create electrochemical proton gradient across the vacuolar membrane to energize substrate transport in and out of the vacuole [12,13]. In addition, V-PPase was suggested to have a higher vacuolar acidification potential compared to V-ATPase and also contribute to energize various transporters, such as Ca2+/H+, Na+/H+ and Zn2+/H+ exchangers and phosphate transporter, at the vacuolar membrane [14]. The pH of various cellular compartments is associated with the activities of proton pumps and transporters that transport substrates in exchange of H+.

Phytohormone transporters, alkaloid transporters, ion and ion chelator transporters, sugar transporters, and amino acid transporters are common active transporters in plants. Examples of phytohormone transporters, alkaloid transporters, and ion and ion chelator transporters include ATP-binding cassette (ABC) transporters and Multidrug Additionally, Toxic compound Extrusion (MATE) transporters, while examples of sugar transporters include MonoSaccharide Transporters (MSTs) and SUcrose Transporters (SUTs). These transporters have been reported to play important roles in various biological processes including cellular detoxification, nutrient transport, and stress adaptation. Previous reports have largely focused on the transport of substrates such as metabolites, sugars, and amino acids by these transporters. However, considering the mechanics of the transport activities, the protons required in exchange of these substrates also deserve the same attention. The awareness of the role of protons, and therefore pH, in transport activities will bring forth a more comprehensive understanding of these transporters.
