한빛사논문
- 조회329
Sujin Kim,1,12 Keonyong Lee,1,12 Yong Seok Choi,2 Jayoung Ku,1 Hyeonkyeong Kim,5,6 Raisa Kharbash,1 Jimin Yoon,1 Yong Seuk Lee,7 Jin-Hong Kim,5,6,8 Yun Jong Lee,3,4,* and Yoosik Kim1,9,10,11,13,*
1Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
2Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam 13605, South Korea
3Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea
4Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea
5Center for RNA Research, Institute for Basic Science, Seoul 08826, South Korea
6Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, South Korea
7Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea
8Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 08826, South Korea
9KAIST Institute for Health Science and Technology (KIHST), KAIST, Daejeon 34141, South Korea
10KAIST Institute for BioCentury, KAIST, Daejeon 34141, South Korea
11BioProcess Engineering Research Center and BioInformatics Research Center, KAIST, Daejeon 34141, South Korea
12These authors contributed equally
13Lead contact
*Correspondence
Abstract
Protein kinase R (PKR) is an immune response protein that becomes activated by double-stranded RNAs (dsRNAs). PKR overactivation is associated with degenerative diseases with inflammation, including osteoarthritis (OA), but the dsRNA activator remains largely unknown. Here, we find that mitochondrial dsRNA (mt-dsRNA) expression and its cytosolic efflux are facilitated in chondrocytes under OA-eliciting conditions, leading to innate immune activation. Moreover, mt-dsRNAs are released to the extracellular space and activate Toll-like receptor 3 at the plasma membrane. Elevated levels of mt-dsRNAs in the synovial fluids and damaged cartilage of OA patients and in the cartilage of surgery-induced OA mice further support our data. Importantly, autophagy prevents PKR activation and protects chondrocytes from mitochondrial stress partly by removing cytosolic mtRNAs. Our study provides a comprehensive understanding of innate immune activation by mt-dsRNAs during stress responses that underlie the development of OA and suggests mt-dsRNAs as a potential target for chondroprotective intervention.
논문정보
- Research article
- 2022년 08월 (BRIC 등록일 2022-10-13)
- 국내 연구진
- 생명과학 > 분자생물학
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