Iron Fist: When Biology Meets Fiction

Celine Caseys
Plant Cell Extracts
4 min readApr 8, 2019

by Céline Caseys

Super heroes are everywhere these days: Comics, TV shows, movies. Did you ever wonder which super powers are pure fiction and which approach real biological fact?

While some super heroes, such as batman or iron man rely directly on technology; others are inspired by science and biology. For example, the basic premise of genetic mutation such as in the X-men is definitely a biological fact, but in fictional stories, the effects of mutations are amplified to unrealistic proportions. Spiderman’s qualities are also based on biological facts, such as the extreme strength of the spider silk and the exceptional hunting skills of spiders.

The art of cellular Kung Fu

Marvel’s Iron Fist hero as represented by Martin Cruz Romero

Iron Fist is a Marvel comic that was first published in the 1970s, and recently released as a TV show. The hero’s super strength comes from his ability to summon his chi (described as a life force energy) into his fist. This ‘Iron Fist’ can strike as a powerful weapon and sometimes a force of destruction.

Marvel’s Iron fist comic was inspired by Chinese culture and martial art. However, beyond the mystical aspects of the chi, martial art visual and strength symbolism associated to iron, it has a biological equivalent that happens at a much smaller scale within cells. However, rather than concentrating “chi”, cells actually import iron (and oxygen) to create powerful weapons in biological reality. This cellular “Iron Fist’ is called ferroptosis [1].

Ferroptosis, a form of cellular “Kung Fu” happening within cells. Illustration adapted from Mohamed Hassan and brgf.

This form of “cellular kung fu” happens in your body; in your cells.

The mechanism for ferroptosis was discovered just 6 years ago by researchers at Columbia University while testing chemicals for their pharmaceutical potential in killing cells. These researchers found a novel path to cell death and discovered that cells in difficult conditions can summon iron and toxic chemicals called reactive oxygen species. Normally, cells export these unstable wastes to avoid their toxic effects. However, cells that are in trouble do the opposite: they send signals for an influx of toxins.

Iron reacts with certain oxygen-based toxins and starts a chain of chemical reactions that produces even more toxins. The resulting toxicity is like a powerful punch to the cell. It is so violent that it breaks down cell’s inner tissues and the cell dies.

This biological ‘kung fu’ strategy may read like a scary story, but cell death is a normal process, and cells that fail to die can lead, for example, to cancer.

While ferroptosis is under investigation for its high potential in medicine, as a cellular mechanism it can have applications beyond human medicine. In a recent Plant Cell publication, Korean researchers showed that this new form of cell death is involved in plant defense in rice [2].

The fight against the shadows

In the ‘Iron Fist’ fiction, the hero fights criminal organizations that secretly infiltrate communities. These organizations work hard to be invisible within cities as their best defense policy is to remain in the shadows.

Once again, real biological strategies overlap with the adventures of superheroes. In nature, Magnaporthe oryzae, a pathogenic fungus, use the same ‘shadow’ strategy when invading rice leaves. This pathogen invades and lives within the plant cells, feeding off the plant’s nutrients. To remain under the radar, the fungus manipulates information within the cell to hide its presence to the plant. If detected, its survival is compromised.

Like many hidden threats, Magnaporthe is not to be underestimated as an opponent. This microscopic fungus causes worldwide rice production losses that could feed 60 million people every year. Thankfully for us, hungry humans, some plants are naturally resistant to this fungus. However, up to recently, how these resistant rice plants manage to fight back against Magnaporthe was largely unknown.

Rice cells under attack by Magnaporthe as observed under a microscope with different staining technics. From top to bottom: normal view; green fluorescence; iron staining; cell death staining. The bar represents 20um. Reproduced from Figure 1 from Dangol et al., 2019, Plant Cell.

It is know that rice cells have “sentinel proteins” that monitor the cell and send distress signals when danger is detected. Some pathogens are well-equipped to recognize the cell reactions and rapidly block these distress signals. The immune response to the invasion is then weak and short and the pathogen has no problem surviving it.

Dangol and coauthors [2] showed that when the fungus fails to remain undetected, the rice plant cells have activated ferroptosis. This violent reaction knocks the fungus dead. It also kills the plant cell under invasion, but it effectively stops the spread of pathogen and limits the loss of nutrients for neighboring cells.

The discovery of this new cellular Kung Fu move gives researchers some ideas on how to fight pathogens. Rice is so far the only plant shown to know this defensive move, but chances are high that other crops kick pathogens the same way. Plants may not have shiny super powers but they can play the heroes too.

Céline Caseys

Department of Plant Sciences

University of California, Davis

celcaseys@ucdavis.edu

Orcid: 0000–0003–4187–9018

Twitter: C_Caseys

References:

[1] Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, … and Stockwell BR. (2012). Ferroptosis: an iron dependent form of nonapoptotic cell death. Cell 149: 1060 -1072.

[2] Dangol S, Chen Y, Hwang BK, Jwa NS. (2018). Iron and Reactive Oxygen Species Dependent Ferroptotic Cell Death in Rice Magnaporthe oryzae Interactions. Plant Cell https://doi.org/10.1105/tpc.18.00535

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Celine Caseys
Plant Cell Extracts

Plant-Curious Biologist. I study and write about plant interactions. I'm currently postdoctoral researcher at UC Davis Plant Sciences