Abstract P2025: Aminoacyl-trna Synthetase Complex-interacting Multifunctional Protein 3 (aimp3) Is A Key Regulator Of Cardiac Homeostasis

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In eukaryotes, a group of aminoacyl-tRNA synthetases evolved to form a complex thought to facilitate protein synthesis by efficiently providing charged tRNAs to the translating ribosome. The human muti-synthetase complex consists of 8 aminoacyl-tRNA synthetases and 3 non-enzymatic proteins known as aminoacyl-tRNA synthetase complex-interacting multifunctional proteins (AIMP1, 2, and 3). Aside from their role in translation, these multifunctional proteins are involved in other biological processes such as inflammation, apoptosis, and DNA damage response. However, their functions in specialized cells such as cardiomyocytes have not been studied. Here, we report that cardiomyocyte-specific conditional knockout (cKO) of AIMP3 in mice leads to lethal cardiomyopathy, which presents with severe systolic dysfunction, fibrosis, and inflammation. Cardiomyocytes from AIMP3 cKO mice show no change in global protein synthesis, suggesting that AIMP3 plays a critical translation-independent role. Proteomics and oxygen consumption analyses reveal a defect in mitochondrial activity and energy metabolism with ablation of AIMP3. Altogether, we highlight the importance of AIMP3 for the preservation of heart function.

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