复原体促进了mtDNA的溶酶体循环
Parisa Kakanj1,2, Mari Bonse3,4, Arya Kshirsagar5
1Institute of Genetics, University of Cologne, Cologne, Germany.
Science advances
|April 4, 2025
概括
线粒体DNA (mtDNA) 损伤会触发一种质量控制途径. 溶解体和逆转激素复合物有助于清除受损的mtDNA,恢复线粒体功能.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 遗传学 是一个遗传学.
背景情况:
- 线粒体DNA (mtDNA) 易受细胞损伤的影响.
- 复制压力可能导致mtDNA转移到内分体中进行降解.
研究的目的:
- 为了研究响应mtDNA复制压力的细胞机制.
- 为了确定参与线粒体质量控制和mtDNA周转的蛋白质.
主要方法:
- 在mtDNA压力期间绘制蛋白质相互作用的近距离生物化.
- 使用Drosophila模型对mtDNA (ΔmtDNA) 进行长期删除.
- 研究了逆转激素复合物的作用,特别是VPS35.5.
主要成果:
- mtDNA压力重新连接线粒体蛋白质组,增加与溶酶体和囊泡蛋白质的关联.
- 通过VPS35的逆转激素复合物提取线粒体组件,并促进线粒体衍生的囊泡到 lysosomes.
- 在依赖BAX的方式中,mtDNA直接运送到回收器官.
- ΔmtDNA激活特定的转录组以抵消损伤,Vps35表达恢复mtDNA同质体.
结论:
- 一个新的质量控制机制存在于线粒体矩阵.
- 溶解体在mtDNA循环和减轻mtDNA损伤方面发挥着至关重要的作用.
- 逆转激素复合体对于线粒体质量控制和mtDNA循环是必不可少的.
相关概念视频
Export of Misfolded Proteins out of the ER
3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K
Translocation of Proteins into the Mitochondria
3.0K
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,...
3.0K
Mitochondrial Membranes
6.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
6.6K
Mitochondria
9.0K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
9.0K
Non-LTR Retrotransposons
11.3K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.3K
Mitochondrial Protein Sorting
4.1K
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...
4.1K


