An eel’s glow could illuminate liver disease

Fluorescent protein binds to bilirubin, a compound the body must eliminate

Japanese freshwater eels (one shown) travel for miles during migration from the sea to rivers. A protein made by the eels glows when connected to bilirubin, an antioxidant. Together the two compounds may protect the eels' muscles from stress. 

Akiko Kumagai and Atsushi Miyawaki

An eel protein that shines green could enable a new test for liver problems and jaundice. The protein gets its glow on by connecting with the pigment bilirubin, scientists report in the June 20 Cell.

THAR SHE GLOWS A protein in the muscles of Japanese freshwater eels glows green (transverse section shown) when it meets the compound bilirubin, a breakdown product of red blood cells. Scientists have used a lab-made version of the protein to measure bilirubin levels in blood, a good indicator of liver function. Ryoko Ando and Atsushi Miyawaki

Led by bioimaging specialist Atsushi Miyawaki, scientists from the RIKEN research institute in Japan spent three years trying to figure out what switched on the protein’s glow in the species Anguilla japonica. Eventually, the scientists hit upon jaundice-causing bilirubin, a yellowish pigment that’s produced when the hemoglobin in red blood cells breaks down.

The body has bilirubin-eliminating machinery, but when it malfunctions — or in the case of newborns, has yet to turn on — bilirubin levels can soar, causing jaundice, brain damage or even death. By exploiting bilirubin’s ability to turn on the eel protein, Miyawaki and his colleagues developed a simple test with a lab-made version of the protein that uses the brightness of green fluorescence to indicate a blood sample’s level of the pigment.

“What they’ve got is really good,” says bilirubin researcher Stanley Lo of Children’s Hospital of Wisconsin in Milwaukee. “There’s quite a bit to do before it’s in clinical use, but I’d like to see what happens.”

The protein, called UnaG (for unagi, the Japanese word for freshwater eel, and G for green), might also prove useful as a lab tool for illuminating other molecules or whole cells. Unlike many other fluorescent compounds, UnaG can glow in low- or no-oxygen environments, which might make it useful for studying tumors.

Several freshwater eel species make UnaG, which is the first fluorescent protein discovered in a vertebrate, Miyawaki says. The researchers suspect that it plays a role in muscle physiology during eel growth. As youngsters, eels undergo an intense period of migrating between ocean and river, transforming from slender, translucent “glass eels” to hefty, opaque adults. But UnaG’s precise job is unknown. “It is still a riddle — it’s an enigma,” Miyawaki says.

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