https://ror.org/00hj8s172 Department of Biological Sciences, Columbia University, New York, NY, USA.
https://ror.org/036rp1748 Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil.
Life Sci Alliance. 2023 Aug 21;6(11). doi: 10.26508/lsa.202301965. Print 2023 Nov.
The Cox6 subunit of cytochrome oxidase (COX) and the Atp9 subunit of the ATP synthase are encoded in nuclear and mitochondrial DNA, respectively. The two proteins interact to form Atco complexes that serve as the source of Atp9 for ATP synthase assembly. To determine if Atco is also a precursor of COX, we pulse-labeled Cox6 in isolated mitochondria of a nuclear mutant with in mitochondrial DNA. Only a small fraction of the newly translated Cox6 was found to be present in Atco, which can explain the low concentration of COX and poor complementation of the mutation by the allotopic gene. This and other pieces of evidence presented in this study indicate that Atco is an obligatory source of Cox6 for COX biogenesis. Together with our finding that mutants fail to assemble COX, we propose a regulatory model in which Atco unidirectionally couples the biogenesis of COX to that of the ATP synthase to maintain a proper ratio of these two complexes of oxidative phosphorylation.
细胞色素氧化酶（COX）的 Cox6 亚基和 ATP 合酶的 Atp9 亚基分别由核 DNA 和线粒体 DNA 编码。这两种蛋白质相互作用形成 Atco 复合物，作为 ATP 合酶组装的 Atp9 来源。为了确定 Atco 是否也是 COX 的前体，我们在一个具有突变的核突变体的分离线粒体中脉冲标记 Cox6。发现新翻译的 Cox6 只有一小部分存在于 Atco 中，这可以解释 COX 浓度低和 allotopic 基因对突变的互补性差的原因。本研究提出的这一和其他证据表明，Atco 是 Cox6 用于 COX 生物发生的必需来源。结合我们发现突变体无法组装 COX 的结果，我们提出了一个调节模型，其中 Atco 单向将 COX 的生物发生与 ATP 合酶的生物发生偶联起来，以维持这两种氧化磷酸化复合物的适当比例。
