Because the plant cell wall provides the first line of defence 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 (CSCs) from the plasma membrane in Arabidopsis thaliana, resulting in anisotropic cell elongation and a weak cell wall. Surprisingly, in addition to mutations in CELLULOSE SYNTHASE 1 (CESA1) and CELLULOSE SYNTHASE 3 (CESA3), a forward genetic screen identified two independent defective genes encoding pentatricopeptide repeat (PPR)-like proteins [CELL WALL MAINTAINER 1 (CWM1) and 2 (CWM2)] 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 signalling, 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, and constitutive activation of mitochondrial retrograde signalling resulted in tolerance towards C17. The C17 tolerance of cwm2 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.