Role of human HSPE1 for OPA1 processing independent of HSPD1.
Role of human HSPE1 for OPA1 processing independent of HSPD1.
复制标题
DOI：
10.1016/j.isci.2023.106067
复制
发表时间：
2023-02-17
期刊：
影响因子：
5.8
通讯作者：
Sesaki, Hiromi
中科院分区：
文献类型：
--
作者：
Yeung, Nelson;Murata, Daisuke;Iijima, Miho;Sesaki, Hiromi
人类mtHSP60/HSPD1-mtHSP10/HSPE1系统防止蛋白质错误折叠，并维持线粒体基质中的蛋白质稳定。这种伴侣系统的活动变化与人类疾病有关，如癌症和神经退行性变。然而，HSPD1和HSPE1中的缺陷如何影响线粒体的结构和动力学仍然是个谜。在目前的研究中，我们在人类细胞系HEK293T中解决了这个基本问题。我们发现，HSPD1或HSPE1的缺失会导致线粒体的碎片化，这表明线粒体融合减少。支持这一观点的是，HSPE1的耗尽导致OPA1的蛋白水解性失活，OPA1是一种与动力蛋白相关的GTPase，融合在线粒体膜上。这种OPA1的失活是由一种应激激活的金属蛋白酶OMA1介导的。相反，HSPD1缺失并未诱导OMA1激活或OPA1裂解。这些数据表明，HSPE1通过一种独立于其伴侣活性的机制控制线粒体的形态。HSPE1的缺失导致OPA1的切割，而不依赖于HSPD1。HSPD1和HSPE1的缺失降低了呼吸活性。OMA1在OPA1的切割中起一定的作用
The human mtHSP60/HSPD1-mtHSP10/HSPE1 system prevents protein misfolding and maintains proteostasis in the mitochondrial matrix. Altered activities of this chaperonin system have been implicated in human diseases, such as cancer and neurodegeneration. However, how defects in HSPD1 and HSPE1 affect mitochondrial structure and dynamics remains elusive. In the current study, we address this fundamental question in a human cell line, HEK293T. We found that the depletion of HSPD1 or HSPE1 results in fragmentation of mitochondria, suggesting a decrease in mitochondrial fusion. Supporting this notion, HSPE1 depletion led to proteolytic inactivation of OPA1, a dynamin-related GTPase that fuses the mitochondrial membrane. This OPA1 inactivation was mediated by a stress-activated metalloprotease, OMA1. In contrast, HSPD1 depletion did not induce OMA1 activation or OPA1 cleavage. These data suggest that HSPE1 controls mitochondrial morphology through a mechanism separate from its chaperonin activity. Depletion of HSPE1 results in the cleavage of OPA1 independent of HSPD1 HSPD1 and HSPE1 depletion decreases respiration activity OMA1 plays a role in OPA1 cleavage from HSPE1 depletion The mobile loop region of HSPE1 is required to rescue OPA1 cleavage Biological sciences; Molecular biology; Cell biology
登录
查看更多内容
影响因子：
5
作者：
Dorn, Gerald W., II
通讯作者：
Dorn, Gerald W., II
影响因子：
19
作者：
Kameoka S;Adachi Y;Okamoto K;Iijima M;Sesaki H
通讯作者：
Sesaki H
影响因子：
17.1
作者：
Acin-Perez, Rebeca;Victoria Lechuga-Vieco, Ana;Antonio Enriquez, Jose
通讯作者：
Antonio Enriquez, Jose
影响因子：
3.3
作者：
Lee B;Ahn Y;Kang SM;Park Y;Jeon YJ;Rho JM;Kim SW
通讯作者：
Kim SW
影响因子：
5
作者：
Bie AS;Fernandez-Guerra P;Birkler RI;Nisemblat S;Pelnena D;Lu X;Deignan JL;Lee H;Dorrani N;Corydon TJ;Palmfeldt J;Bivina L;Azem A;Herman K;Bross P
通讯作者：
Bross P