RESPARA · Impact of mitochondrial respiration efficiency on plant cell metabolism
FP7 — People (Marie Curie Actions)
- Duration
- 2010-04-01 → 2014-03-31
- EU contribution
- €100,000
- Participants
- 2
- Scheme
- MC-IRG
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Results in brief
Impact of mitochondrial respiration efficiency on plant cell metabolism
Respiration is an essential cellular metabolic pathway that provides energy to fuel housekeeping cellular functions and growth. Respiration is composed of three pathways, the glycolysis degrading sugars, the TCA cycle metabolises sugar by-products to produce redox energy that will be used by the oxidative phosphorylation (OXPHOS) system to convert ADP into ATP. The reactions leading to ATP synthesis are well understood but the mechanisms involved in the regulation of this pathway remain unclear. In addition to the ATP production, the respiratory activity influences other metabolic pathways. However, it is unknown if the respiratory activity can actively or passively modulate the cellular metabolism. Two hypotheses have been formulated to explain how respiratory activity affects cellular metabolic reactions. As the main ATP producing pathway, respiration has a direct impact on the ATP/ADP ratio and on the activity of enzymes using ATP. This control of enzyme activity by the ATP/ADP ratio is known as the adenylate control. Besides, the OXPHOS system is producing reactive oxygen species (ROS) when electrons are lost. As ROS accumulation causes a modification of the redox status, the modulation of cellular metabolism by the activity of the OXPHOS system via ROS/redox signaling is another possibility. This project aimed to understand how the respiratory chain contributes to the control of plant metabolism. To achieve this goal, we used mutants in the first complex of the OXPHOS system, complex I, in the model plant Arabidopsis thaliana. Complex I is not described as essential for plant growth but complex I mutants show a growth retardation. We built a collection of complex I mutants and identified strong and mild mutants based on the severity of the growth phenotype. We characterized these mutants using a systems biology approach, which explores steady-state levels, to identify the mitochondrial signal(s) triggering a cellular response, hypothesizing that the strong mutants should express stronger signals. However this approach did not yield the expected outcome as the mutants studied, despite showing severe phenotypic differences, were found to be extremely similar at a molecular level. However, an intensive characterization of the mutants allowed the identification of differences in fluxes through the respiratory pathway between strong and mild complex I mutants. In addition, our work shows that complex I is essential for a key development step. In conclusion, during the course of this project we showed that complex I is essential for survival in plants as it is in mammals. In addition, we showed that in the absence of complex I, respiration fluxes are impaired, suggesting that complex I acts as a negative regulator of respiration. This finding, if it is confirmed in humans, could be the basis of the development of new treatment strategies to cure the multiple diseases caused by complex I deficiency.
Data: CORDIS, © European Union
Project objective
Respiration plays a key role in the survival of aerobic organisms since it is providing ATP, the energy for the whole cell. The reactions leading to the synthesis of ATP are well known but the mechanisms by which mitochondrial respiration controls cellular functions is unknown, mainly because most mutants in respiratory enzymes are lethal. Two hypotheses have been formulated to explain how respiration activity affects the metabolism. As the product of respiration is ATP, the respiration rate has an impact on the ATP/ADP ratio and on the activity of enzymes using ATP. This control of enzyme activity by the ATP/ADP ratio is known as the adenylate control. Besides, the mitochondrial electron transfer chain (ETC) is producing reactive oxygen species (ROS) when electrons are lost during their transfer through the ETC. As ROS accumulation causes a modification of the redox status and triggers the reorganisation of cellular activity, therefore the influence of ETC activity on cellular metabolism via ROS signalling is another possibility. In plants, most of the mutants with impaired respiration are affected in complex I, the first enzyme of the ETC. These mutants have reduced ATP synthesis and enhanced stress tolerance, indicating that both the adenylate control and the ROS signalling are affected. This project aims to understand how respiration contributes to the control of plant metabolism. Several complex I mutants which possess different levels of remaining complex I activity are available in Arabidopsis. The production of ATP and ROS by the ETC will be investigated to characterise the respiratory defect caused by the reduction in complex I function. System biology approaches including transcriptomic and metabolomic will be use to highlight the mitochondrial signals causing a cellular response and elucidate the corresponding pathways with a special attention to the adenylate control and the ROS signalling pathway.
Original text from CORDIS.
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Data: CORDIS, © European Union