**5. Perspectives**

The transport activities of many plant MCs have been characterized in vitro [11,12]; however, most are yet to be interrogated *in planta*. Specifically, transporters such as DICs, SFC, and DTC, which have been shown to transport TCA cycle intermediates in vitro, have not had their physiological functions clearly elucidated *in planta*. A common feature is their broad substrate specificities in vitro. Whether a more stringent gating mechanism exists *in planta* is one of the more interesting questions. Thus far, there is no experimental evidence regarding how these transporters might impact cellular respiration, carbon metabolism, or cellular redox poise. For example, 2-OG shuttling is critical as it integrates carbon and nitrogen metabolism [39,40], while data indicates that some MCs interact with TCA cycle enzymes [31,32]. To date, the physiological significance of these potential protein–protein interactions is yet to be elucidated. Perhaps, these MCs participate in the formation of TCA metabolon serving as membrane anchors. Data from yeast MPCs suggested that formation of complexes modulate transporter activity. Whether canonical MCF members' activity can also be modulated by the formation of protein complexes and by extension, impose a stricter substrate specificity is an attractive area of research. Recently, it was shown that the transport activity of the human CiC seemed to be modulated via acetylation of a lysine residue in response to glucose supply [94]. Moreover, the transport activity of the rat carnitine/acylcarnitine carrier was shown to be modulated by glutathionylation [95]. It will be interesting to ascertain how other post-translational modifications might modulate MC transport activity and whether this can also be observed *in planta*. More recently, it was shown the circadian protein CLOCK (Circadian Locomotor Output Cycles Kaput) was found to bind the human and mouse DIC, suggesting that a possible connection between circadian rhythm and mitochondrial metabolism may be mediated by dicarboxylate carriers [96]. To date, there have been no such reports on the connection between plant circadian rhythm and plant MCs and how this might be relevant in the diurnal regulation of plant metabolism. While these questions are no doubt interesting, the major challenge in our understanding of the function of these carriers is presented by their apparent functional redundancy. This feature renders it difficult to tease apart their physiological function—the broader adoption of CRISPR/Cas9 based approaches in plants [97] and natural variance screening methods [98] may address this challenge. That said, we still lack biochemical data for many of the members of the plant MCF. It is likely that only as a result of data coming from multiple approaches, we will be able to fully comprehend their physiological importance in the regulation of plant central carbon metabolism.

**Author Contributions:** M.R.T., Y.Z. and A.R.F. conceived the topic and wrote the manuscript. T.N. and M.R.T. did the phylogenetic analysis. T.N., J.L.H., and A.R.F. edited and provided valuable comments to improve the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** M.R.T. is supported by the Melbourne-Potsdam PhD Program (MelPoPP). T.N. is supported by the International Max Planck Research School 'Primary Metabolism and Plant Growth' (IMPRS-PMPG) PhD program. A.R.F. and Y.Z. would like to thank the European Union's Horizon 2020 research and innovation program, project PlantaSYST (SGA-CSA No. 739582 under FPA No. 664620) for supporting their research. J.L.H. is supported by an Australian Research Council Discovery Project [DP180102630].

**Conflicts of Interest:** The authors declare no conflict of interest.
