The metabolic imbalance underlying lesion formation in Arabidopsis thaliana overexpressing farnesyl diphosphate synthase (isoform 1S) leads to oxidative stress and is triggered by the developmental decline of endogenous HMGR activity.

Overexpression of Arabidopsis thaliana farnesyl diphosphate synthase isoform 1S (FPS1S) in transgenic A. thaliana (L.) Heynh. leads to necrotic lesion formation in leaves in planta and to premature senescence in detached leaves [A. Masferrer et al. (2002) Plant J 30:123-132]. Here we report that leaves of plants overexpressing FPS1S with symptoms of necrosis show increased H2O2 formation and induction of both the pathogenesis-related 1 (PR-1) and the alternative oxidase 1a (AOX1a) genes. These findings indicate that plants overexpressing FPS1S should be considered as lesion-mimic mutants and lead us to propose that H2O2 is the main inducing agent of necrosis in these plants. The onset of necrosis appears in a developmentally regulated manner that correlates with the developmental decline of endogenous 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity. Accordingly, constitutive overexpression of HMGR in plants overexpressing FPS1S prevents both necrosis and premature senescence. These observations demonstrate that both phenotypes are due to an insufficient supply of mevalonic acid and support the notion that the metabolic imbalance associated with FPS1S overexpression is, in fact, triggered by the developmental decline of HMGR activity. We also show that overexpression of FPS1S alleviates growth inhibition caused by overexpression of the catalytic domain of isoform HMGR1S. Overall, our results reinforce the view that the levels of specific intermediates of the mevalonic acid pathway must be strictly controlled, particularly those located at branch-point positions, in order to avoid deleterious effects on plant growth and development.