Researchers report that pheomelanin — the pigment behind orange-red hair and some bird feathers — may help protect cells by using up excess cysteine, which can be toxic in surplus. In experiments on 65 zebra finches, blocking pheomelanin synthesis with ML349 while increasing cysteine led to greater cellular damage, suggesting the pigment converts surplus cysteine into an inert form. The results, published in PNAS Nexus, point to a possible metabolic benefit that could help explain why pheomelanin-promoting genes persist despite links to higher melanoma risk.
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New research suggests the gene that produces orange-red hair in some people may also have a previously unrecognized protective role inside cells. The pigment pheomelanin, responsible for red and orange hues in human hair and some bird feathers, is made using the amino acid cysteine. While excess cysteine can be toxic, converting it into pigment could help cells avoid damage.
What the study did
Scientists published their findings in PNAS Nexus after using a recently discovered molecule, ML349, which blocks pheomelanin synthesis. They tested 65 adult zebra finches, a bird species whose orange beaks contain pheomelanin, splitting them into treatment and control groups to probe the pigment's physiological role.
Key findings
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Male finches that received dietary cysteine together with ML349 (which prevents pheomelanin formation) experienced more pronounced cellular damage than males that received extra cysteine alone. Female finches fed additional cysteine without the blocker also tended to show higher levels of cell damage compared with controls. The pattern suggests pheomelanin synthesis helps maintain safe cysteine levels by converting surplus cysteine into an inert pigment deposited in keratinous structures such as feathers.
"These findings represent the first experimental demonstration of a physiological role for pheomelanin," the authors write in PNAS Nexus.
Why it matters
For years, researchers have been puzzled by the persistence of genes that promote pheomelanin production — including those that cause orange or red hair — because prior work linked pheomelanin to an increased melanoma risk even without UV exposure. This study proposes a trade-off: pheomelanin may carry a long-term cancer risk but also provide a metabolic benefit by preventing cysteine toxicity. The findings improve understanding of pheomelanin's role in cysteine homeostasis and suggest environmental or dietary factors that alter cysteine availability might influence related disease risks.
Limits and next steps
These experiments were conducted in zebra finches; while the biochemical mechanisms are suggestive, further research in mammalian models and human tissues is needed to confirm whether the same protective effect occurs in people. Future studies should explore how dietary cysteine, genetic background, and environment interact with pheomelanin synthesis and melanoma risk.
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