Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins.
Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins.
复制标题
DOI：
10.1083/jcb.200605043
复制
发表时间：
2006-07-31
期刊：
影响因子：
--
通讯作者：
Koehler CM
中科院分区：
文献类型：
--
作者：
Claypool SM;McCaffery JM;Koehler CM
tafazzin （Taz1p）是与Barth综合征（BTHS）相关的突变基因产物，在已发现的28个点突变中，没有一个具有生化解释。在本研究中，内源性Taz1p定位于线粒体，并与面向膜间隙（IMS）的线粒体内外膜相关。出乎意料的是，Taz1p不包含跨膜（TM）片段。相反，Taz1p膜结合涉及一个整合到膜双分子层而不是穿过膜双分子层的片段。预测为TM结构域的残基215-232，通过模拟发生在该片段内保守残基上的四个不同的BTHS突变，被确定为界面膜锚点。每个Taz1p突变体表现出改变的膜关联，并且没有功能。然而，Taz1p功能障碍的基础分为以下两类：(1)错误靶向线粒体基质或(2)与异常复合物组装相关的正确定位。因此，BTHS可能是由改变线粒体内Taz1p分选和组装的突变引起的，这表明Taz1p的脂质靶标位于面向ims的小叶上。
None of the 28 identified point mutations in tafazzin (Taz1p), which is the mutant gene product associated with Barth syndrome (BTHS), has a biochemical explanation. In this study, endogenous Taz1p was localized to mitochondria in association with both the inner and outer mitochondrial membranes facing the intermembrane space (IMS). Unexpectedly, Taz1p does not contain transmembrane (TM) segments. Instead, Taz1p membrane association involves a segment that integrates into, but not through, the membrane bilayer. Residues 215–232, which were predicted to be a TM domain, were identified as the interfacial membrane anchor by modeling four distinct BTHS mutations that occur at conserved residues within this segment. Each Taz1p mutant exhibits altered membrane association and is nonfunctional. However, the basis for Taz1p dysfunction falls into the following two categories: (1) mistargeting to the mitochondrial matrix or (2) correct localization associated with aberrant complex assembly. Thus, BTHS can be caused by mutations that alter Taz1p sorting and assembly within the mitochondrion, indicating that the lipid target of Taz1p is resident to IMS-facing leaflets.
登录
查看更多内容
DOI：
10.1083/jcb.93.1.97
发表时间：
1982-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujiki Y;Hubbard AL;Fowler S;Lazarow PB
通讯作者：
Lazarow PB
影响因子：
4.8
作者：
Claypool, SM;Dickinson, BL;Blumberg, RS
通讯作者：
Blumberg, RS
影响因子：
30.8
作者：
Bione, S;DAdamo, P;Toniolo, D
通讯作者：
Toniolo, D
影响因子：
4.4
作者：
BARTH, PG;SCHOLTE, HR;SOBOTKAPLOJHAR, MA
通讯作者：
SOBOTKAPLOJHAR, MA
影响因子：
4.2
作者：
Barth, PG;Wanders, RJA;Baas, F
通讯作者：
Baas, F