Mitochondrial Defects Confer Tolerance against Cellulose Deficiency

Abstract

Because the plant cell wall provides the first line of defense against biotic and abiotic assaults, its functional integrity needs to be maintained under stress conditions. Through a phenotype-based compound screening approach, we identified a novel cellulose synthase inhibitor, designated C17. C17 administration depletes cellulose synthase complexes from the plasma membrane in , resulting in anisotropic cell elongation and a weak cell wall. Surprisingly, in addition to mutations in () and , a forward genetic screen identified two independent defective genes encoding pentatricopeptide repeat (PPR)-like proteins ( [] and ) as conferring tolerance to C17. Functional analysis revealed that mutations in these PPR proteins resulted in defective cytochrome c maturation and activation of mitochondrial retrograde signaling, as evidenced by the induction of an alternative oxidase. These mitochondrial perturbations increased tolerance to cell wall damage induced by cellulose deficiency. Likewise, administration of antimycin A, an inhibitor of mitochondrial complex III, resulted in tolerance toward C17. The C17 tolerance of was partially lost upon depletion of the mitochondrial retrograde regulator ANAC017, demonstrating that ANAC017 links mitochondrial dysfunction with the cell wall. In view of mitochondria being a major target of a variety of stresses, our data indicate that plant cells might modulate mitochondrial activity to maintain a functional cell wall when subjected to stresses.

Plant Chemical Genetics: From Phenotype-Based Screens to Synthetic Biology

“…A phenotypic screen utilizing ploidy level measurements to find novel cell division-interfering compounds identified the compound C17, which increased polyploidy as a result of cytokinesis inhibition. Interestingly, C17 was further characterized as a cellulose synthase inhibitor that also interfered with mitochondrial retrograde signaling (Hu et al, 2016). Another chemical screen for inhibitors of the lignin biosynthetic pathway based on reduced lignin accumulation in the presence of the cellulose synthesis inhibitor isoxaben revealed 39 small molecules that cause major perturbations in the phenylpropanoid pathway.…”

“…A screen for resistance to the ethylene biosynthesis inhibitor acsinone7303 detected 19 Arabidopsis mutants, designated revert to eto1, of which two carried mutations in the CELLULOSE SYNTHASE6 (CESA6) and DET2 genes, but none were direct targets (Chen et al, 2013). Similarly, in addition to mutations in CESA1 and CESA3, a forward genetic screen found two independent defective genes that encode pentatricopeptide repeat-like proteins and confer tolerance to C17 (Hu et al, 2016).…”

“…One compound was processed in plant cells to p-iodobenzoic acid, which was further characterized as a new inhibitor of cinnamate 4-hydroxylase, a key enzyme of the phenylpropanoid pathway for the synthesis of the lignin polymer building blocks (Van de Wouwer et al, 2016). Overall, chemical screens designed to identify cell wall modifiers have yielded useful molecules, although several interesting compounds have been discovered through unrelated phenotype-based screens, such as screening for trafficking or ploidy modifiers (Worden et al, 2015;Hu et al, 2016).…”

“…In general, two types of libraries can be distinguished: large, often combinatorial libraries, such as the Chembridge DIVERSet library; and more focused collections, such as the LATCA (Hicks and Raikhel, 2012). By far, the most used library in plant chemical biology is the Chembridge DIVERSet (Armstrong et al, 2004;Zouhar et al, 2004;Surpin et al, 2005;DeBolt et al, 2007;Rojas-Pierce et al, 2007;Christian et al, 2008;Gendron et al, 2008;Savaldi-Goldstein et al, 2008;De Rybel et al, 2009, 2012Lin et al, 2010;Tsuchiya et al, 2010;Kim et al, 2011;Kerchev et al, 2014;Hu et al, 2016;Van de Wouwer et al, 2016). Chembridge also provides focused or targeted small-molecule libraries (Poretska et al, 2016).…”

A Functional Link between Mitochondria and the Cell Wall in Stress Responses

“…Stresses can also alter mitochondrial function, especially in terms of the rate of respiratory electron transport, and mitochondria are important hubs for signaling to other parts of the cell in response to stress conditions (reviewed in Ng et al, 2014;Huang et al, 2016). Now, Hu et al (2016) establish that not only are both compartments involved in stress responses, there is a functional connection between mitochondrial function under stress and cell wall integrity.…”