When plants are subjected to stressful situations, such as diseases, extreme changes in temperature, scarcity of nutrients or water, the concentration of oxygen in plant cells decreases, inducing a state known as hypoxia. This triggers a cascade of chemical reactions in the cells that are intended to allow the organism to survive adversity.

It has been shown that a protein present in the inner membrane of plant mitochondria, UCP1 (uncoupling protein 1, mitochondrial uncoupling protein 1) is the trigger that triggers this response to hypoxia.

The discovery paves the way for the development of more resistant plants to extreme environmental conditions, such as those resulting from climate change.

Mitochondrial genomic DNA codes for less than 1% of its many proteins; therefore, mitochondria depend on the nuclear genome to remotely regulate their function. This interaction between the nucleus and the mitochondria requires signaling between compartments, which can be retrograde (from mitochondria to nucleus) or anterograde (nucleus to mitochondria), which acts to adjust organelle function during development and in response to environmental stresses.

Mitochondrial retrograde signaling is a cimportant component of intracellular stress signaling in eukaryotes. UCP1 is an abundant plant inner mitochondrial membrane protein with multiple functions including uncoupled respiration and amino acid transport, which broadly influence responses to abiotic stress.

Although The mechanisms through which this retrograde function acts are unknown., the overexpression of UCP1 activates the expression of nuclear genes associated with hypoxia, functioning as a trigger in the activation of this response. This explains why plants that express this protein at high levels are more tolerant to a wide range of biotic and abiotic stresses.

Several extramitochondrial factors that play a role in retrograde and anterograde signaling have been identified to regulate plant signaling, such as the enzyme specific alternative oxidase (AOX) and other nuclear-encoded mitochondrial proteins. In various taxa of flowering plants, overexpression of UCP1 together with AOX decreases the release of reactive oxygen species (ROS) by the mitochondria, protecting plants from multiple stresses and resulting in extensive alteration of the transcriptome of nuclear origin that, interestingly, includes the activation of hypoxia.

Plants have an oxygen sensing mechanism that involves the O2 (molecular oxygen) dependent destruction of Cys-amino-terminal protein substrates (cysteine ​​at the amino terminus of the peptide chain) via the plant cysteine ​​oxidase network ( plant cysteine ​​oxidase, PCO), and the main substrates of the pathway are ethylene response transcription factors (ERFVII). Under conditions of low oxygen level, ERFVII are stabilized due to the inhibition of PCO activity, which results in the induction of the expression of several genes, including those related to hypoxia.

On the other hand, it was verified that UCP1 functions as a switch in the chain of metabolic responses related to the hypoxia response. The protein acts on a specific group of transcription factors that have the amino acid cysteine ​​at the N-terminus and functions as a mitochondrial sensor. If the oxygen content is low, UCP1 prevents the cysteine ​​oxidation of the transcription factors that control the hypoxia response, activating them. These transcription factors, when activated, 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 deactivated (*).

In addition to advancing knowledge about the functions of UCP1, this discovery paves the way for the development of agricultural crops that are tolerant to the stress imposed by climate change.

(*) The transcription factors that allow the expression of genes involved in the events resulting from ethylene and hypoxia are inactive if the cysteine ​​at the -NH2 end is oxidized (this amino acid has sulfur in the form of sulfhydryl -SH). The UCP1 protein helps to prevent this oxidation when the oxygen content is low since it “detects” the level of this gas.