Fusion of protein aggregates facilitates asymmetric damage segregation.
Fusion of protein aggregates facilitates asymmetric damage segregation.
复制标题
DOI：
10.1371/journal.pbio.1001886
复制
发表时间：
2014-06
期刊：
影响因子：
9.8
通讯作者：
Tolić IM
中科院分区：
文献类型：
--
作者：
Coelho M;Lade SJ;Alberti S;Gross T;Tolić IM
Fusion of harmful aggregated proteins into larger clumps increases the asymmetry of segregation of damage at cell division, favoring the production of rejuvenated cells. Asymmetric segregation of damaged proteins at cell division generates a cell that retains damage and a clean cell that supports population survival. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, segregation of damaged proteins is achieved by retention and active transport. We have previously shown that in the symmetrically dividing Schizosaccharomyces pombe there is a transition between symmetric and asymmetric segregation of damaged proteins. Yet how this transition and generation of damage-free cells are achieved remained unknown. Here, by combining in vivo imaging of Hsp104-associated aggregates, a form of damage, with mathematical modeling, we find that fusion of protein aggregates facilitates asymmetric segregation. Our model predicts that, after stress, the increased number of aggregates fuse into a single large unit, which is inherited asymmetrically by one daughter cell, whereas the other one is born clean. We experimentally confirmed that fusion increases segregation asymmetry, for a range of stresses, and identified Hsp16 as a fusion factor. Our work shows that fusion of protein aggregates promotes the formation of damage-free cells. Fusion of cellular factors may represent a general mechanism for their asymmetric segregation at division. During their lifetime, cells accumulate damage that is inherited by the daughter cells when the mother cell divides. The amount of inherited damage determines how long the daughter cell will live and how fast it will age. We have discovered fusion of protein aggregates as a new strategy that cells use to apportion damage asymmetrically during division. By combining live-cell imaging with a mathematical model, we show that fission yeast cells divide the damage equally between the two daughter cells, but only as long as the amount of damage is low and harmless. However, when the cells are stressed and the damage accumulates to higher levels, the aggregated proteins fuse into a single clump, which is then inherited by one daughter cell, while the other cell is born clean. This form of damage control may be a universal survival strategy for a range of cell types, including stem cells, germ cells, and cancer cells.
登录
查看更多内容
DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR
影响因子：
2
作者：
Bolte, S;Talbot, C;Satiat-Jeunemaitre, B
通讯作者：
Satiat-Jeunemaitre, B
影响因子：
3.3
作者：
Chen, DR;Toone, WM;Bähler, J
通讯作者：
Bähler, J
DOI：
10.1073/pnas.0804550105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Erjavec, N.;Cvijovic, M.;Nystrom, T.
通讯作者：
Nystrom, T.
影响因子：
64.5
作者：
Caudron, Fabrice;Barral, Yves
通讯作者：
Barral, Yves