线粒体RNA的细胞溶液泄漏驱动SASP
Stella Victorelli1,2, Madeline Eppard3,4, Hélène Martini3,4
1Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. Victorelli.Stella@mayo.edu.
Nature communications
|December 15, 2025
概括
线粒体RNA (mtRNA) 激活衰老细胞中的炎症反应,驱动衰老和组织功能障碍. 抑制mtRNA泄漏和相关的RNA传感器可以减少老化相关的分泌表型 (SASP).
科学领域:
- 细胞衰老 细胞衰老
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 衰老细胞释放因子 (SASP),导致组织功能障碍和衰老.
- 线粒体功能障碍和线粒体DNA (mtDNA) 的释放激活cGAS/STING通路,导致SASP.
- 其他线粒体成分在SASP中的作用不太清楚.
研究的目的:
- 研究线粒体RNA (mtRNA) 在诱导SASP中的作用.
- 确定mtRNA泄漏发生的机制.
- 探索针对老化中的mtRNA的治疗策略.
主要方法:
- 衰老细胞培养和细胞质RNA的分析.
- 对RNA传感器RIG-I,MDA5和MAVS的激活试验.
- 抑制RNA传感器和BAX/BAK的作用.
- 对SASP因子表达的评估.
- 在体内研究中,使用一种与代谢功能障碍相关的脂肪肝炎 (MASH) 的小鼠模型.
主要成果:
- 线粒体RNA (mtRNA) 在衰老细胞的细胞质中积累.
- mtRNA激活了RIG-I和MDA5,导致了MAVS聚合和SASP诱导.
- 抑制RNA传感器或删除BAX和BAK可以显著减少SASP.
- 在衰老过程中,BAX和BAK对mtRNA泄漏至关重要.
结论:
- 线粒体RNA (mtRNA) 是老化相关分泌表型 (SASP) 的关键调解者.
- mtRNA的BAX/BAK依赖性泄漏激活了RNA感知通路,促进了炎症.
- 准mtRNA泄漏和RNA传感器为MASH等与年龄相关的炎症性疾病提供了潜在的治疗途径.
更多相关视频
05:52Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
2.9K
09:21Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity
Published on: October 22, 2018
9.5K
相关概念视频
Translocation of Proteins into the Mitochondria
11.8K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
11.8K
Energy to Drive Translocation
2.6K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.6K
ATP Synthase: Mechanism
16.6K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
16.6K
Mitochondrial Protein Sorting
5.6K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
5.6K
Leaky Scanning
5.6K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.6K
Nonsense-mediated mRNA Decay
11.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
11.6K
