Mitochondrial function is critically dependent on the folding of the mitochondrial inner membrane into cristae; indeed, numerous human diseases are associated with aberrant crista morphologies. With the MICOS complex, OPA1 and the F₁F_o‐ATP synthase, key players of cristae biogenesis have been identified, yet their interplay is poorly understood. Harnessing super‐resolution light and 3D electron microscopy, we dissect the roles of these proteins in the formation of cristae in human mitochondria. We individually disrupted the genes of all seven MICOS subunits in human cells and re‐expressed Mic10 or Mic60 in the respective knockout cell line. We demonstrate that assembly of the MICOS complex triggers remodeling of pre‐existing unstructured cristae and de novo formation of crista junctions (CJs) on existing cristae. We show that the Mic60‐subcomplex is sufficient for CJ formation, whereas the Mic10‐subcomplex controls lamellar cristae biogenesis. OPA1 stabilizes tubular CJs and, along with the F₁F_o‐ATP synthase, fine‐tunes the positioning of the MICOS complex and CJs. We propose a new model of cristae formation, involving the coordinated remodeling of an unstructured crista precursor into multiple lamellar cristae.

中文翻译：

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MICOS组件控制线粒体内膜的重塑和cr连接的重新分布，以介导cr的形成。

线粒体功能关键取决于线粒体内膜折叠成cr状。实际上，许多人类疾病都与异常的crista形态有关。有了MICOS复合物，OPA1和F ₁ F _o- ATP合酶，已经确定了ista生物发生的关键因素，但对其相互作用的了解却很少。利用超分辨率光和3D电子显微镜，我们剖析了这些蛋白质在人类线粒体中ista的形成中的作用。我们分别破坏了人类细胞中所有七个MICOS亚基的基因，并在各自的基因敲除细胞系中重新表达了Mic10或Mic60。我们证明了MICOS复合体的组装触发了先前存在的非结构化cr和从头的重塑在现有网点上形成网点连接（CJ）。我们显示，Mic60-亚复合物足以形成CJ，而Mic10-亚复合物可控制层状cr生物发生。OPA1可稳定管状CJ，并与F ₁ F _o -ATP合酶一起微调MICOS复合体和CJ的位置。我们提出了一种新的缝隙形成模型，涉及将非结构化的缝隙前体协调改造为多个层状缝隙。