Research can contribute to the development of drought-resistant plants and also new treatments for human diseases
Um article published on February 2nd in the magazine Current Biology demonstrated that a protein present in the internal membranes of mitochondria is the trigger that sends a signal to the cell nucleus when the plant is subjected to stress. Stress often generates a situation of low oxygen concentration in cells (hypoxia). Mitochondrial uncoupling protein 1 (UCP1) has a more important role in plant metabolism than previously thought. Its role in plants' response to situations of drought, cold and nutrient scarcity was already known, but the discovery opens up possibilities for developing plants that are more resistant to extreme environmental conditions, such as those resulting from climate change. The research was carried out by scientists from Genomics Research Center Applied to Climate Change (GCCRC), a joint initiative between Embrapa and the Center for Molecular Biology and Genetic Engineering (CBMEG) at Unicamp, supported by Fapesp, in partnership with scientists from the University of Nottingham, in the United Kingdom.
Uncoupling proteins are located in the inner membrane of the mitochondria, in animal and plant cells, and have functions associated with cellular respiration and energy production. However, when the organism is subjected to stressful situations - lack of nutrients, diseases, extreme changes in temperature, scarcity of water - the oxygen concentration decreases, triggering a response mechanism to these adverse conditions. The activation of the response to hypoxia causes a cascade of cellular chemical reactions that aim to overcome these adversities. The discovery of oxygen sensors in human cells, which activate the hypoxia response, yielded the Nobel Prize for William Kaelin Jr, Peter Ratcliffe and Gregg Semenza in 2019. Research on the response to hypoxia in human cells has guided studies aimed at developing treatments for various diseases, including cancer.
The mechanisms that control oxygen signaling in humans and plants have important similarities, but are not controlled by the same proteins. Pedro Barreto, author of the study developed in hispost doctoral (funded by FAPESP), states that, despite being distinct mechanisms, UCP1 is capable of altering the way cells perceive oxygen in both organisms, which raises hypotheses about a conserved function of UCP1 in mitochondrial signaling in response to intracellular oxygen.
Another fact already known in relation to UCP1 in animal cells is the abundance of this protein in mitochondria from the brown adipose tissue of hibernating mammals, such as polar bears. In this case, the protein acts to regulate temperature, helping to produce energy in the form of heat and keeping them warm during the winter.
Researchers at GCCRC and the University of Nottingham were able to demonstrate that UCP1 functions as a trigger in activating the response to hypoxia. This explains why plants that express this protein at high levels are more tolerant to a wide range of biotic and abiotic stresses.
Seeking to understand the role of UCP1 in plants, GCCRC researchers noticed that tobacco plants, when they produce high levels of UCP1, showed high expression of stress-responsive genes, including transcription factors involved in the response to hypoxia. These plants became tolerant to environmental stresses, had an increase in the rate of photosynthesis and an increase in fruit size. “This is a general stress response mechanism that is induced by UCP1”, explains Paulo Arruda, professor at Unicamp and corresponding author of the study.
In this new work, the researchers demonstrated that UCP1 functions as a switch in the chain of metabolic responses related to the response to hypoxia. The protein acts on a specific group of transcription factors that have the amino acid cysteine at one end. “The UCP works as a mitochondrial sensor. If there is little oxygen, UCP1 prevents the oxidation of cysteine in the transcription factors that control the response to hypoxia, activating them. These transcription factors then induce the expression of a wide range of nuclear-encoded genes that contribute to cell survival. In the presence of higher levels of oxygen, the terminal cysteines of these transcription factors are oxidized and they are deactivated”, explains Arruda.
In addition to improving knowledge about the functions of UCP1, the discovery opens the way for the development of agricultural crops tolerant to the stresses imposed by climate change. But it also indicates that the functions of UCP1 in other eukaryotes, such as humans, are broader than previously thought. “It's a general mechanism, and when basic cellular mechanisms are present in practically all eukaryotes, it means that it is an important mechanism for survival'', explains Arruda.
The presence of mitochondrial uncoupling protein was discovered by Brazilian scientist Aníbal Vercesi and collaborators in 2001. Vercesi, to whom Arruda dedicates the work, had formulated the hypothesis that the presence of UCP1 in plants could indicate the protein's relationship with plant thermal regulation (as in hibernating mammals), enabling the development of genetically modified plants cold resistant. The hypothesis has not yet been confirmed, but it suggested ways to investigate the protein, which is now known to be present in many different organisms, with only part of its functions known.
From now on, the challenge is to understand whether this broad response to hypoxia related to UCP1 in plants is also present in animals, and how it could be involved, for example, in the development of cancer.
Article:
Pedro Barreto, Charlene Dambire, Gunjan Sharma, Jorge Vicente, Rory Osborne, Juliana Erika de Carvalho Teixeira Yassitepe, Daniel J. Gibbs, Ivan G. Maia, Michael J. Holdsworth and Paulo Arruda. Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway. Current Biology 32, 1–9, 2022. https://doi.org/10.1016/j.cub.2022.01.037
About the GCCRC
The Genomics Research Center for Climate Change (GCCRC) is located at the Center for Molecular Biology and Genetic Engineering (CBMEG), at Unicamp. The center is a partnership between Embrapa and Unicamp and is financed by FAPESP through the Engineering Research Centers program. The GCCRC aims to develop technologies to increase plant tolerance to the stresses imposed by global climate change. Learn more
