Matrix Redox Physiology Governs the Regulation of Plant Mitochondrial Metabolism through Post-Translational Protein Modifications

ABSTRACT Mitochondria function as hubs of plant metabolism. Oxidative phosphorylation produces ATP, but it is also a central high-capacity electron sink required by many metabolic pathways that need to be flexibly coordinated and integrated. We here review redox-associated post-translational protein modifications (PTMs) that implement a very significant proportion of mitochondrial metabolic regulation. We conclude that: (i) The major redox couples in the mitochondrial matrix - NAD, NADP, thioredoxin, glutathione and ascorbate - are in kinetic steady-state rather than thermodynamic equilibrium. (ii) Targeted proteomics have produced long lists of proteins potentially regulated by Cys oxidation/Trx, Met-SO formation, phosphorylation, or Lys acetylation. At this point, we only understand the functional importance of relatively few of these PTMs and some of the site modifications may represent 9molecular noise9 caused by spurious reactions. (iii) Different PTMs on the same protein or on different proteins in the same metabolic pathway can interact to fine-tune the regulation. (iv) PTMs take part in repair of stress-induced damage, e.g. by reduction of Met and Cys oxidation products, but also in adjusting metabolic functions in response to environmental variation, like changes in light irradiance or oxygen availability. (v) Together, the PTMs form a multidimensional regulatory system that provide essential speed and flexibility to mitochondrial coordination, beyond what can be regulated by changes in nuclear gene expression alone.