A Failure Mode and Effect Analysis of plant metabolism reveals why cytosolic fumarase is required for temperature acclimation in Arabidopsis

Plants acclimate their photosynthetic capacity in response to changing environmental conditions. In Arabidopsis thaliana, photosynthetic acclimation to cold requires the accumulation of the organic acid fumarate, catalysed by a cytosolic fumarase FUM2, however the role of this is currently unclear. In this study, we use an integrated experimental and modelling approach to examine the role of FUM2 and fumarate across the physiological temperature range. Using physiological and biochemical analyses, we demonstrate that FUM2 is necessary for acclimation not only to low temperatures, as previously shown, but also to increased temperature. To understand the role of FUM2 activity, we have adapted a reliability engineering technique, Failure Mode and Effect Analysis (FMEA), to apply it to a biological problem. This allows us to formalize a rigorous approach for ranking metabolites according to the potential risk they pose to the metabolic system. FMEA identifies fumarate as a low-risk metabolite. Its precursor, malate, is shown to be high-risk and liable to cause system instability. We conclude that the role of cytosolic fumarase, FUM2, is to provide a fail-safe, maintaining system stability under changing environmental conditions.