AIMP3 Protein Crucial for Cardiac Function and Survival

AIMP3 (ARS-interacting multifunctional protein 3) plays an essential role for accurate protein translation in the heart, according to research published in Nature Cardiovascular Research. The findings could inform new treatments for heart disease.

“AIMP3 is a protein that had never been studied in the heart and was of unclear function,” said study author Federica Accornero, PhD, an associate professor of molecular biology, cell biology, and biochemistry at Brown University, in a news release. “What we discovered is that cardiac AIMP3 is crucial for survival.”

Previous studies proposed AIMP3 anchors methionyl tRNA synthetase (MetRS), which is key to initiating protein synthesis as well as adding methionine internally during protein elongation, in a multisynthetase complex.

The researchers found that knocking out AIMP3 specifically in cardiomyocytes of mice led to severe heart problems, including inflammation, scarring, and fatal heart failure.

They discovered that MetRS localization and global protein synthesis were unaffected in the AIMP3-knockout mouse and instead that AIMP3 was essential for homocysteine editing by MetRS. Without AIMP3, homocysteine, an intermediate produced during the metabolism of methionine, accumulates and induces the production of reactive oxygen species, protein aggregation, mitochondrial dysfunction, autophagy, and ultimately cell death.

“Overall, we uncovered a unique role of AIMP3 in maintaining the editing activity of MetRS and its essential role in heart function and survival,” said lead author Anindhya Das, PhD, a postdoctoral research associate in molecular biology, cell biology, and biochemistry at Brown, in the news release.

“The heart is a critical system to study, because there isn’t really an effective strategy to repair injury,” added Dr Accornero. “So, the maintenance of the health of these cardiac cells is a really critical point.”

Their findings could lead to new treatments for heart diseases linked to homocysteine buildup.

Disclosure(s):

The authors declare no competing interests.