对与衰老相关的蛋白质结构变化的全球分析揭示了基于酶聚合的长寿控制
Jurgita Paukštytė1, Rosa María López Cabezas1, Yuehan Feng2
1Helsinki Institute of Life Science, HiLIFE, University of Helsinki, 00790 Helsinki, Finland; Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland.
Molecular cell
|September 12, 2023
概括
细胞衰老会改变蛋白质结构,影响细胞功能,导致疾病. 科学家绘制了酵母中的这些蛋白质变化,确定了谷氨酸合成酶聚合作为一个关键的衰老机制,可以准延长寿命.
科学领域:
- 分子生物学分子生物学
- 老年学是一门学科.
- 蛋白质组学是指蛋白质组学.
背景情况:
- 衰老导致由蛋白质变化驱动的渐进的细胞表型变化.
- 了解与年龄相关的蛋白质结构和功能变化对于解决与年龄相关的疾病至关重要.
- 对这些变化及其对衰老表型的贡献的全面知识仍然有限.
研究的目的:
- 对早期与年龄相关的蛋白质结构变化进行全蛋白质组分析.
- 为了确定受细胞衰老过程中结构变化影响的特定蛋白质和途径.
- 阐明与年龄相关的表型背后的机制,并探索潜在的干预措施.
主要方法:
- 利用有限的蛋白解质质谱法 (LiP-MS) 进行全蛋白质组分析,分析老化的发芽酵母中的蛋白质结构变化.
- 将结果汇编到 ProtAge 在线目录中,以提供可访问性和进一步研究.
- 研究了已识别的蛋白质的机制性作用,专注于谷氨酸合成酶 (Glt1) 聚合.
主要成果:
- 揭示了关键细胞调节者的与年龄相关的功能变化,包括那些参与翻译,蛋白质折叠和氨基酸代谢的功能变化.
- 发现谷氨酸合成酶 (Glt1) 在衰老过程中聚合成超分子自我组装,破坏氨基酸平衡.
- 证明通过突变抑制Glt1聚合可逆转氨基酸不平衡,减少线粒体功能障碍,并延长老化细胞的寿命.
结论:
- 这项研究提供了与年龄相关的酵母蛋白质结构变化的全面地图.
- 确定了Glt1聚合作为一种新的机制,有助于表型的衰老.
- 准Glt1聚合是一种潜在的策略,可以缓解与年龄相关的衰退并延长寿命.
相关概念视频
01:26Aging
86
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
86
01:26Bacterial Protein Maturation
36
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
36
01:19The Effect of Aging on Tissues
2.1K
Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
2.1K
01:37Mitochondria
13.7K
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,...
13.7K