Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species
Abstract
Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on aging remains elusive. Here, we show that Pelota, the ribosome rescue factor, promotes longevity and protects against age-related pathological phenotypes in multiple metazoan species. By performing a targeted genetic screen, we find that Pelota is indispensable for longevity in the nematode Caenorhabditis elegans . We show that Pelota mitigates premature senescence in cultured human cells, muscle aging in mice, and neuropathology in cellular and organoid models of Alzheimer’s disease. Mechanistically, we demonstrate that Pelota maintains autophagy-mediated proteostasis, by preventing the hyperactivation of mechanistic target of rapamycin signaling. Overall, our work highlights the conserved functional significance of RQC, regulated by Pelota, in extending lifespan and protecting diverse species against age-associated disease phenotypes.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (30)
Jongsun Lee
Bora Lee
Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology
Hyein Lee
Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology
Eun Ji E. Kim
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Sieun S. Kim
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Hyunwoo C. Kwon
Hanseul Lee
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Gee-Yoon Lee
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Woojin Hong
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Seokjin Ham
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Jae Won Yang
Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology
Heeju Park
Department of Biological Sciences, Ulsan National Institute of Science and Technology
Tatiana M. Moreno
Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute
Michelle E. Brown
Sanford Burnham Prebys Medical Discovery Institute
Hae-Eun H. Park
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Eunah Kim
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Yoonji Jung
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Eunseok Kang
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Sangsoon Park
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Yeo Jin Shin
Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology
Seokjun G. Ha
Sujeong Kwon
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Seungjae Hwang
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Hyemin Min
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Caroline Kumsta
Sanford Burnham Prebys Medical Discovery Institute
Chunghun Lim
Department of Biological Sciences, Korea Advanced Institute of Science and Technology
Chanhee Kang
School of Biological Sciences, Seoul National University, Gwanak-gu
Jinsoo Seo
Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology
Kwang-Pyo Lee
Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology
Seung-Jae V. Lee