TOR is a kinase that controls cell growth in response to nutrients such as nitrogen. It was discovered through the use of rapamycin, an antibiotic that blocks its action. Since this discovery, several studies have indicated that TOR has a key role in the process of cell growth and division in all eukaryotes (organisms composed of cells that each contain a nucleus). TOR is practically omnipresent in the living world, regulating the growth of a vast array of organisms, from fungi to humans.
In “TOR Signaling and Nutrient Sensing”, published in the Annual Review of Plant Biology, researchers from several countries, including two from Brazil, Camila Caldana and Michel Vincentz, highlight the role of TOR in the regulation of vital processes.
Caldana is affiliated with the National Bioethanol Science & Technology Laboratory (CTBE), which belongs to the National Energy & Materials Research Center (CNPEM) in Campinas, São Paulo State. Vincentz is a professor at the University of Campinas’s Biology Institute (IB-UNICAMP). Both receive support from FAPESP for their research.
Caldana’s project (http://www.bv.fapesp.br/en/auxilios/58413/) entitled “Regulation of plant growth by the target of rapamycin (TOR) pathway” is funded by FAPESP under the Young Investigators in Emerging Institutions Program.
Vincentz has a regular grant from FAPESP for the project entitled “Defining the architecture of the gene regulatory network related to AtbZIP63”.
“Integration between environmental signals, such as water, nutrients, temperature and light, and intracellular processes, such as cell growth and metabolism, is a condition for life. Cells must respond appropriately to the environment to survive and multiply. One of the signaling pathways that ensures this integration involves TOR,” Vincentz told Agência FAPESP.
“If the environmental factors are favorable, this pathway is triggered so that cell multiplication and growth can occur. When the environmental factors become unfavorable, it’s interrupted and other pathways are activated, including one controlled by the kinase SnRK1, which has an antagonistic function. This preserves energy metabolism until favorable conditions return.”
To take only two among many possible examples, TOR participates in both the growth of both plants and cancer cells. Enhancing growth in plants is of considerable interest because it promotes higher crop yield and biomass production. In cancer, however, the goal is to develop drugs that inhibit cell multiplication. Hence, it is important to study the actions of these kinases, as well as their targets and antagonists, in depth.
“TOR promotes growth, and SnRK1 limits growth by making the plant redirect its metabolism and tap into its reserves,” Caldana said. “Our studies show that these two antagonistic kinases play key roles in the balanced use of carbon and in energy metabolism, among other processes. Hence, there is strong interest in understanding how the two pathways interact.”
In recent experiments, the two researchers obtained mutants of the model plant Arabidopsis thaliana by conditionally silencing TOR. Conditional silencing is a procedure that controls gene expression in terms of time and quantity. TOR inhibition changed energy, lipid and carbon metabolism by causing a buildup in amino acids, starch and triacylglycerides.
“Through this system, it’s possible to control a plant’s growth until it reaches a given biomass. Once this stage is reached, silencing followed by metabolic reprogramming could result in the production and accumulation of sources of sugars potentially involved in several aspects of yield,” Caldana said.
“An understanding of the mechanisms that control the appropriate allocation of carbon for growth optimization in a fluctuating environment opens up perspectives for the manipulation of carbohydrate conversion routes, allowing us to develop agricultural techniques and technologies that are more efficient and that respect the natural environment in the context of climate change.”