The synthesis of Cox1, the conserved catalytic-core subunit of Complex IV, a multi-subunit machinery of the mitochondrial oxidative phosphorylation (OXPHOS) system under environmental stress is not sufficiently addressed. In this study, we show that the putative YihA superfamily GTPase, Mrx8 is a bonafide mitochondrial protein required for Cox1 translation initiation and elongation during suboptimal growth condition at 16°C. Mrx8 was found in a complex with mitochondrial ribosomes, consistent with a role in protein synthesis. Cells expressing mutant Mrx8 predicted to be defective in guanine nucleotide binding and hydrolysis were compromised for robust cellular respiration. We show that requirement of Pet309 and Mss51 for cellular respiration is not bypassed by overexpression of Mrx8 and vice versa. Consistently the ribosomal association of Mss51 is independent of Mrx8. Significantly, we find that GTPBP8, the human orthologue, complements the loss of cellular respiration in Δmrx8 cells and GTPBP8 localizes to the mitochondria in mammalian cells. This strongly suggest a universal role of MRX8 family of proteins in regulating mitochondrial function.

Cox1 的合成，复合物 IV 的保守催化核心亚基，环境压力下线粒体氧化磷酸化 (OXPHOS) 系统的多亚基机器，尚未得到充分解决。在这项研究中，我们展示了假定的 YihA 超家族 GTPase，Mrx8 是在 16°C 的次优生长条件下 Cox1 翻译起始和延伸所需的真正线粒体蛋白。Mrx8 在与线粒体核糖体的复合物中被发现，与蛋白质合成中的作用一致。表达突变体 Mrx8 的细胞预测在鸟嘌呤核苷酸结合和水解方面存在缺陷，但由于细胞呼吸强劲而受到损害。我们表明，Mrx8 的过度表达不会绕过 Pet309 和 Mss51 对细胞呼吸的要求，反之亦然。Mss51 的核糖体结合始终独立于 Mrx8。值得注意的是，我们发现GTPBP8是人类直系同源物，补充了Δmrx8细胞中细胞呼吸的丧失，并且 GTPBP8 定位于哺乳动物细胞中的线粒体。这有力地表明了MRX8蛋白家族在调节线粒体功能中的普遍作用。