Spatial orchestration of mitochondrial translation and OXPHOS complex assembly
Spatial orchestration of mitochondrial translation and OXPHOS complex assembly
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DOI：
10.1038/s41556-018-0090-7
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发表时间：
2018-05-01
影响因子：
21.3
通讯作者：
Jakobs, Stefan
中科院分区：
文献类型：
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作者：
Stoldt, Stefan;Wenzel, Dirk;Jakobs, Stefan
氧化磷酸化（OXPHOS）对于真核细胞中绝大多数ATP的再生至关重要（1）。OXPHOS由嵴膜中的大型多亚基蛋白复合物进行，嵴膜是线粒体内膜的内陷。OXPHOS复合物是在核和线粒体基因组中编码的亚基的混合物。因此，这些双源复合物的组装对细胞来说是一个巨大的后勤挑战。使用超分辨率显微镜（纳米显微镜）和定量冷冻免疫金电子显微镜，我们确定了特定的转录翻译和不同的装配步骤的双源复合物在酵母酿酒酵母发生。我们的数据表明，复合物III和复合物IV的蛋白质优先插入内膜的不同位点，而不是复合物V。我们进一步证明，早期，而不是晚期，组装步骤的复合物III和复合物IV优先发生在内界膜。相比之下，所有步骤的复杂V组装主要发生在嵴膜。因此，OXPHOS复合物的组装是空间上精心策划的，可能代表了线粒体生物发生中一个不受重视的调控层。
Oxidative phosphorylation (OXPHOS) is vital for the regeneration of the vast majority of ATP in eukaryotic cells(1). OXPHOS is carried out by large multi-subunit protein complexes in the cristae membranes, which are invaginations of the mitochondrial inner membrane. The OXPHOS complexes are a mix of subunits encoded in the nuclear and mitochondrial genomes. Thus, the assembly of these dual-origin complexes is an enormous logistical challenge for the cell. Using super-resolution microscopy (nanoscopy) and quantitative cryo-immunogold electron microscopy, we determined where specific transcripts are translated and where distinct assembly steps of the dual-origin complexes in the yeast Saccharomyces cerevisiae occur. Our data indicate that the mitochondrially encoded proteins of complex III and complex IV are preferentially inserted in different sites of the inner membrane than those of complex V. We further demonstrate that the early, but not the late, assembly steps of complex III and complex IV occur preferentially in the inner boundary membrane. By contrast, all steps of complex V assembly occur mainly in the cristae membranes. Thus, OXPHOS complex assembly is spatially well orchestrated, probably representing an unappreciated regulatory layer in mitochondrial biogenesis.