LA JOLLA (October 14, 2026)—Energy production in our cells, oxygen traveling in our blood, and immune cells fighting infection all depend on iron, an essential mineral that enters the food chain when plants absorb it from soil. But iron is often scarce—likely increasingly so as global weather and temperatures continue to change—and we aren't the only ones that need it.
Microbes that live on and around plants also need iron. Plants are then forced to strike a delicate balance between using iron to defend themselves against microbes and retaining it to maintain health. New Salk research reveals a dual-purpose protein called SRF3, which both restores iron balance after microbial invasion and simultaneously ensures that the plant's immune response is just right.
The study, published in Science Advances on October 14, 2026, and funded by both federal research grants from the National Institutes of Health and private philanthropy, provides crucial insights into plant resilience that could shape future agricultural efforts to feed a growing global population with nutritious crops.
Why are iron and immunity connected?
"Because plants are the main entry point for iron into our food supply, understanding how they control iron is important not only for plant health but also for agriculture and human nutrition," says co-corresponding author Wolfgang Busch, PhD , a professor and holder of the Hess Chair in Plant Science at Salk.
Busch, alongside co-corresponding author Matthieu Pierre Platre, PhD, have been studying how plants control iron for a while. The two published a paper together in Nature Communications in 2022, in which they first identified SRF3 as mediating plant responses to microbes.
SRF3 lives on the surface of plant cells. There, it is firmly anchored in the plasma membrane, the cell's outermost wall, where it can receive environmental cues and signals. The 2022 Salk study revealed that SRF3 could sense iron levels and direct root growth accordingly and suggested that the SRF3 protein is also involved in nutritional immunity responses.
"It became very interesting because microbes and plants are fighting for limited iron in the soil," explains Busch. "So, microbes start invading plants to steal iron from their cells, while plants are forced to defend themselves and protect their iron stores. We were really interested in this tug of war."
What was really happening on the molecular level and the mechanisms behind SRF3's involvement remained unknown—until now.
How do plants balance immune defense and iron retention?
The researchers started with Arabidopsis thaliana, a small flowering plant that is easy to grow and acts as a popular laboratory stand-in for other plants, including important crops like wheat or corn. Through a series of experiments—from flagging and tracking iron levels in cells to visualizing the movement of SRF3 to removing SRF3 completely and observing the consequences—they laid out the mechanism by which SRF3 balances immune defense and iron maintenance.
First, SRF3 detects an invading microbe and promotes the generation of reactive oxygen species, molecules that can be used to fight the microbe. While helpful in attacking microbes, the creation of reactive oxygen species eats up cellular iron stores.
As iron levels fall in the cell, SRF3 starts moving around: SRF3 reorganizes itself, receives a key molecular tag called ubiquitin, and is pulled into the cell. Once SRF3 is inside the cell, the creation of new reactive oxygen species that depletes iron and fights microbes stops, and balance is restored.
"What makes this study special is that we explain the mechanism from the single molecule scale to the full organism, providing a level of mechanistic integration that is rarely achievable in other biological systems," says Platre, a former staff scientist in Busch's lab and current research associate at the Institute for Plant Sciences of Montpellier.
Could this change future agricultural practices and biological research?
The implications are two-fold: First, there are the plant-specific findings that could be used to create more nutrient-rich, resilient crops; then, there are the molecular biology findings about surface protein dynamics that could fundamentally change how scientists understand cellular communication.
"In the future, this knowledge could help guide the development of crops that resist disease, grow well, and provide nutritious food," says Busch. "It also suggests that plants use their membranes as sort of computers—turning all these moving molecules out in the environment into actionable signals."
"This idea that cell surfaces are sort of computational hubs was proposed in mammalian cells at first," adds Platre, "and now we are seeing it happening in plant cells. Also, our study is the first to show that ubiquitin molecular tags, which are among the most used protein tags in cells, can be used to reorganize proteins on cell surfaces and change how they respond to their environment."
Future research will explore this "membrane computer" concept further, with the aim of understanding how cells integrate information. The researchers also hope to identify proteins and genes that SRF3 interacts with. By understanding more deeply how plants respond to environmental cues, the findings can help scientists design crops resilient to extreme weather and changing soil nutrition.
Other authors and funding
Other authors include co-first authors Lukas Brent and Matias Gleason of Salk; Preyanka Mehta, Ling Zhang, Olivier Kaakeh, Laura Martins, and Julie Law of Salk; Laia Armengot and Marc Valls of Centre for Research in Agricultural Genomics and Universitat Autònoma de Barcelona; Julie Neveu and Grégory Vert of University of Toulouse; Min Cao of Salk and Fudan University; Santosh Satbhai of Indian Institute of Science Education and Research; and Nuria Coll of Centre for Research in Agricultural Genomics and Consejo Superior de Investigaciones Científicas.
The work was supported by the National Institutes of Health (R01GM127759, P30 CA014195, P30 AG068635, S10 OD021815), Human Frontier Science Program Organization (LT000340/2019 L), Natural Science Foundation of Shanghai (24ZR1404000), Fudan University, Helmsley Center for Genomic Medicine, Chapman Foundation, and Helmsley Charitable Trust.
This press release was written by Isabella Davis.
About the Salk Institute for Biological Studies
The Salk Institute is an independent, nonprofit research institute founded in 1960 by Jonas Salk, developer of the first safe and effective polio vaccine. The Institute's mission is to drive foundational, collaborative, risk-taking research that addresses society's most pressing challenges, including cancer, Alzheimer's, and agricultural vulnerability. This foundational science underpins all translational efforts, generating insights that enable new medicines and innovations worldwide. Learn more at www.salk.edu .
