Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA.
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Cell Chem Biol. 2018 Jun 21;25(6):738-748.e3. doi: 10.1016/j.chembiol.2018.04.002. Epub 2018 Apr 26.
In eukaryotes, mitochondria have been hypothesized to generate sulfur species required for tRNA thiolation in the cytosol, although no direct evidence thus far exists. Here we have detected these sulfur species, making use of our observation that isolated yeast cytosol alone is unable to thiolate tRNAs but can do so upon addition of mitochondria. Mitochondria were found to utilize the cysteine desulfurase Nfs1 to produce sulfur-containing species with masses ranging from 700 to 1,100 Da. Mitochondria exported these species via the Atm1 transporter in the inner membrane. Once exported to the cytosol, these sulfur species promoted cytosolic tRNA thiolation with no further requirement of mitochondria. Furthermore, we found that the Isu1/2 scaffolds but not the Ssq1 chaperone of the mitochondrial iron-sulfur cluster machinery were required for cytosolic tRNA thiolation, and thus the sulfur utilization pathway bifurcates at the Isu1/2 site for intra-organellar use in mitochondria or export to the cytosol.
在真核生物中，人们假设线粒体可以产生细胞质中 tRNA 硫代所需的硫物种，尽管迄今为止还没有直接的证据。在这里，我们检测到了这些硫物种，这是利用我们的观察结果得出的，即单独分离的酵母细胞质本身无法使 tRNA 硫代，但在添加线粒体后可以做到。线粒体被发现利用半胱氨酸脱硫酶 Nfs1 来产生质量范围在 700 到 1100 道尔顿的含硫物种。线粒体通过内膜中的 Atm1 转运蛋白将这些物质输出。一旦被运到细胞质中，这些硫物种就会促进细胞质 tRNA 的硫代，而不再需要线粒体。此外，我们发现，线粒体铁硫簇组装所必需的 Isu1/2 支架而不是 Ssq1 伴侣，对于细胞质 tRNA 的硫代是必需的，因此硫利用途径在 Isu1/2 处分支，用于细胞器内的线粒体使用或输出到细胞质。
