유영범 (한국생명공학연구원(KRIBB), 충남대학교)

한빛사논문

조회434

한국생명공학연구원(KRIBB), 충남대학교

Exp. Mol. Med., 01 April 2024 | https://doi.org/10.1038/s12276-024-01199-x Age-dependent loss of Crls1 causes myopathy and skeletal muscle regeneration failure

Youngbum Yoo ^1,2, MyeongHoon Yeon ¹, Won-Kyung Kim^1,3, Hyeon-Bin Shin ^1,3, Seung-Min Lee ¹, Mee-Sup Yoon ^4,5, Hyunju Ro ² and Young-Kyo Seo ^1,3,6,*

¹Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
²Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
³Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Korea.
⁴Department of Molecular Medicine, College of Medicine, Gachon University College of Medicine, Incheon 21999, Republic of Korea.
⁵Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea.
⁶School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.

^*Corresponding author: correspondence to Young-Kyo Seo

Abstract

Skeletal muscle aging results in the gradual suppression of myogenesis, leading to muscle mass loss. However, the specific role of cardiolipin in myogenesis has not been determined. This study investigated the crucial role of mitochondrial cardiolipin and cardiolipin synthase 1 (Crls1) in age-related muscle deterioration and myogenesis. Our findings demonstrated that cardiolipin and Crls1 are downregulated in aged skeletal muscle. Moreover, the knockdown of Crls1 in myoblasts reduced mitochondrial mass, activity, and OXPHOS complex IV expression and disrupted the structure of the mitochondrial cristae. AAV9-shCrls1-mediated downregulation of Crls1 impaired muscle regeneration in a mouse model of cardiotoxin (CTX)-induced muscle damage, whereas AAV9-mCrls1-mediated Crls1 overexpression improved regeneration. Overall, our results highlight that the age-dependent decrease in CRLS1 expression contributes to muscle loss by diminishing mitochondrial quality in skeletal muscle myoblasts. Hence, modulating CRLS1 expression is a promising therapeutic strategy for mitigating muscle deterioration associated with aging, suggesting potential avenues for developing interventions to improve overall muscle health and quality of life in elderly individuals.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-01)
연구진국내 연구진
분야 생명과학 > 세포생물학

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