When Growth Meets Stress: A Peptide Fine-Tunes Iron Uptake, Growth in Plants

Researchers have identified a novel molecular module, the PEP2-PEPR2 signalling pathway, that regulates iron-deficiency responses in plants. This discovery reveals how plants integrate growth and iron acquisition, offering insights into nutrient homeostasis and potential strategies for improving crop yield and nutritional quality in iron-deficient soils globally.

Anaemia affects around 500 million women aged 15-49 years and 269 million children under five worldwide. In India, which is home to the world’s largest adolescent population, this burden is especially heavy, prompting the country to lead one of the biggest public health campaigns to combat the condition, which continues to impact millions of women, young children, and teenagers.

But the story of iron deficiency does not begin in the human body; it starts in the soil, where plants first absorb the iron that eventually makes its way into the food chain. Plants are the primary source of iron for humans and many animals, whether we eat them directly or consume animals that feed on them.

All our food crops depend on specific environmental conditions that determine how well they can absorb essential nutrients, and iron is one of the most important. Plants need iron for photosynthesis, respiration, and overall growth. Today, climate change, soil degradation, and declining mineral content are making it harder for crops to access this crucial nutrient, posing a growing threat to global food security. To build climate-resilient crops and protect human health, scientists are working to understand how plants detect changes in iron availability and adjust their growth

As iron deficiency affects nearly one-third of agricultural soils globally, researchers have been interested in and focused on understanding how plants react to iron limitation, and have attempted targeted tweaks to enable crops to grow in nutrient-poor soils.

Iron deficiency affects millions of hectares of farmland worldwide (about 13% of agricultural soil in India is iron-deficient). However, unlike other stresses, the role of small signalling peptides in controlling iron acquisition has remained largely unexplored, leaving a major gap in our understanding of plant nutrient-stress responses.

The discovery

We uncovered a novel molecular module that can act as a key regulatory switch determining whether plants trigger or suppress iron-deficiency responses. In plants, iron deficiency triggers a suite of morphological, physiological, and molecular responses aimed at enhancing iron uptake and maintaining homeostasis. These include root-level changes, secretion of compounds to mobilise iron, and activation of specific transcriptional networks. The findings, published recently in New Phytologist, reveal an unexpected but fundamental role for the signalling peptide PEP2 and its receptor PEPR2 in integrating plant growth and iron acquisition.

PEP2 peptide’s role in iron homeostasis

Two genes — Iron Regulated Transporter (IRT1) and Ferric Reduction Oxidase 2 (FRO2) — are classical iron-uptake genes in plants. While FRO2 reduces Fe³⁺ to Fe²⁺, IRT1 transports Fe²⁺ into root cells forming the core of Strategy I iron acquisition. What makes this discovery interesting is that the switch is not a classical Fe-uptake gene such as IRT1 or FRO2. Rather, it is a peptide — damage-associated molecular pattern (DAMP) peptide — previously known for its role in immunity that plays a crucial role. Plants produce PEP2 in response to internal stress or tissue damage, but our study for the first time shows that the peptide also participates directly in nutrient (iron) homeostasis.

Under iron-deficient conditions, the expression of a PEP2 precursor (PROPEP2) is strongly induced, and the mature PEP2 peptide is released into the apoplast — a network of cell walls, intercellular spaces, and xylem vessels in plants. This peptide is then perceived by its primary receptor (PEPR2) on root cells, triggering downstream signalling that profoundly alters the plant’s ability to take up iron.

Understanding the PEP2-PEPR2 pathway’s role

To understand the importance of this pathway, we generated loss-of-function mutants of the PEP2 precursor (PROPEP2). Surprisingly, these mutants showed reduced sensitivity to iron deficiency. They exhibited longer roots, higher rhizosphere acidification, and greater iron accumulation compared to wild-type plants. This clearly revealed that endogenous PEP2 normally functions as a negative regulator of iron uptake, preventing excessive activation of iron deficiency responses.

The most compelling insight came from examining iron uptake genes. Using transcript and protein-level analyses, we found that plants treated with the synthetic PEP2 peptide exhibit strong repression of IRT1 and FRO2, the primary components of the iron acquisition machinery. In parallel, the PEP2 application upregulates BTS, a known negative regulator of iron uptake. These findings validate our hypothesis that PEP2 actively inhibits iron acquisition pathways.

We next investigated how this peptide exerts its influence. Using genetic and cell-biological tools, we demonstrated that PEPR2 is the principal receptor that perceives PEP2 under iron limitation. Plants lacking PEPR2 were largely unresponsive to synthetic PEP2, continuing to grow longer roots and maintaining higher iron content even under iron deprivation. Synthetic PEP2 treatment also increased PEPR2 protein accumulation in iron-starved roots, highlighting dynamic feedback between peptide production and receptor activation.

Together, these results reveal that the PEP2–PEPR2 module operates as a molecular switch, controlling whether plants maintain or suppress Fe uptake during nutrient stress.

Implications of the study

Iron acquisition in plants is controlled by a complex network of transporters, reductases, and regulatory transcription factors. Conventional approaches target individual genes in this network, but are often insufficient because nutrient homeostasis requires coordinated changes across multiple pathways. The PEP2-PEPR2 signalling module, however, provides a single point of control capable of influencing iron uptake, root architecture, rhizosphere acidification, and growth, simultaneously.

This discovery also sheds light on how plants balance growth with stress adaptation. Iron-deficient plants must activate energy-intensive uptake machinery, but doing so excessively can harm growth or disrupt cellular redox balance. The Pep2 peptide appears to buffer this response by preventing runaway iron acquisition, ensuring that plants mobilise iron cautiously while maintaining growth when possible.

Another exciting implication is the connection between immune signalling and nutrient signalling. Peptides like PEP2 were originally believed to function exclusively in defense responses. The discovery that they also regulate nutrient stress responses suggests an intricate crosstalk between immunity, metabolism, and growth. This opens up avenues to explore whether other DAMP peptides control nutrient acquisition in a similar manner.

Since this entire mechanism is regulatory rather than genetic, there is also potential for reversible and tuneable manipulation. Modulating peptide levels in crops and engineering variants of the PEPR receptors might allow farmers and breeders to optimise iron uptake based on local soil conditions, potentially enhancing crop yield in iron-poor soils.

Finally, the knowledge gained from Arabidopsis (a model plant) can be translated to crops such as rice, wheat, and pulses, as many stress-signalling pathways are conserved. With iron deficiency affecting nearly one-third of agricultural soils globally, leveraging peptide-based signalling could significantly improve nutritional quality and yield stability.

A new molecular axis for nutrient resilience

In summary, our work identifies the PEP2–PEPR2 signalling module as a critical regulator of iron-deficiency responses in Arabidopsis. Acting like a master switch, it coordinates iron uptake, root growth, and stress signalling, revealing an unexpected link between DAMP peptides and nutrient homeostasis.

The discovery that a small endogenous peptide can shape plant architecture and nutrient acquisition opens up new horizons in understanding how plants respond to environmental challenges. As climate change intensifies abiotic stresses worldwide, such molecular insights will be key to building future-ready agriculture, where plants can grow, adapt, and thrive even in the most challenging soils.