UMR 866 Dynamique Musculaire et Métabolisme (INRA, Université Montpellier 1, Université Montpellier 2), INRA, Montpellier cedex, France.
J Cell Physiol. 2012 Dec;227(12):3768-77. doi: 10.1002/jcp.24085.
The major effect of T3 on mitochondrial activity has been partly explained by the discovery of p43, a T3-dependent transcription factor of the mitochondrial genome. P43 is imported into mitochondria in an atypical manner which is not yet fully understood. Our aim was to characterize the p43 sequences inducing its mitochondrial import, using in organello import experiments with wild-type or mutated proteins and validation in CV1 cells. We find that several sequences define the mitochondrial addressing. Two alpha helices in the C-terminal part of p43 are actual mitochondrial import sequences as fusion to a cytosolic protein induces its mitochondrial translocation. Helix 5 drives the atypical mitochondrial import process, whereas helices 10/11 induce a classical import process. However, despite its inability to drive a mitochondrial import, the N-terminal region of p43 also plays a permissive role as in the presence of the C-terminal import sequences different N-terminal regions determine whether the protein is imported or not. These results can be extrapolated to other mitochondrial proteins related to the nuclear receptor superfamily, devoid of classical mitochondrial import sequences.
T3 对线粒体活性的主要影响部分可以通过发现 p43 来解释，p43 是一种依赖 T3 的线粒体基因组转录因子。p43 以一种尚未完全理解的非典型方式被导入线粒体。我们的目的是使用野生型或突变蛋白的体外导入实验，并在 CV1 细胞中进行验证，来描述诱导其线粒体导入的 p43 序列。我们发现几个序列定义了线粒体的定位。p43 的 C 端的两个α螺旋是实际的线粒体导入序列，因为与细胞质蛋白融合会诱导其线粒体易位。螺旋 5 驱动非典型的线粒体导入过程，而螺旋 10/11 则诱导经典的导入过程。然而，尽管它不能驱动线粒体导入，但 p43 的 N 端区域也起着允许的作用，因为在存在 C 端导入序列的情况下，不同的 N 端区域决定蛋白质是否被导入。这些结果可以外推到其他与核受体超家族相关的线粒体蛋白，这些蛋白缺乏经典的线粒体导入序列。
