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Redox Biol., Jul 25 2024, 75 S2213-2317(24)00257-X | https://doi.org/10.1016/j.redox.2024.103279
Reduced dynamicity and increased high-order protein assemblies in dense fibrillar component of the nucleolus under cellular senescence
Minjeong Jo a, Soomin Kim a, Jeongeun Park b, Young-Tae Chang c, Youngdae Gwon a,b,d
aDepartment of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea
bDepartment of MetaBioHealth, Sungkyunkwan University Institute for Convergence, Suwon, 16419, Republic of Korea
cDepartment of Chemistry, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea
dKIST-SKKU Brain Research Center, Sungkyunkwan University Institute for Convergence, Suwon, 16419, Republic of Korea
Corresponding author : Youngdae Gwon
Abstract
Cellular senescence, which is triggered by various stressors, manifests as irreversible cell cycle arrest, resulting in the disruption of multiple nuclear condensates. One of the affected structures is the nucleolus, whose tripartite layout, separated into distinct liquid phases, allows for the stepwise progression of ribosome biogenesis. The dynamic properties of dense fibrillar components, a sub-nucleolar phase, are crucial for mediating pre-rRNA processing. However, the mechanistic link between the material properties of dense fibrillar components and cellular senescence remains unclear. We established a significant association between cellular senescence and alterations in nucleolar materiality and characteristics, including the number, size, and sphericity of individual subphases of the nucleolus. Senescent cells exhibit reduced fibrillarin dynamics, aberrant accumulation of high-order protein assemblies, such as oligomers and fibrils, and increased dense fibrillar component density. Intriguingly, the addition of RNA-interacting entities mirrored the diminished diffusion of fibrillarin in the nucleolus during cellular senescence. Thus, our findings contribute to a broader understanding of the intricate changes in the materiality of the nucleolus associated with cellular senescence and shed light on nucleolar dynamics in the context of aging and cellular stress.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-08-08)
- 국내 연구진
- 의약학 > 분자세포의학
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새로운 차원의 노화세포 표현형 규명
성균관대학교 의학과 권영대 교수 연구팀은 노화에 수반되는 세포 내 신규 표현형을 발굴해 냈다고 9일 밝혔다. 노화는 그간 거스를 수 없는 생명 현상으로 여겨졌으나 근래 세포 노화에 대한 연구가 축적되며 인류가 극복할 수 있는 대상으로 인식의 전환이 이루어지고 있다. 세포 노화는 유전체 불안정성, 활성산소종, 만성적 염증 등으로 인해 세포의 증식 능력이 감퇴된 상황이며 알츠하이머 병, 관절염, 망막 변성, 근감소증 등의 퇴행성 노인질환과 밀접한 관계가 있다고 알려져 있다.
- Bio통신원
- 2024. 08. 09
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