Univ. Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.
Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden.
Mol Biol Cell. 2022 Dec 1;33(14):ar130. doi: 10.1091/mbc.E21-10-0499. Epub 2022 Sep 21.
Cytochrome oxidase (CcO) is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of CcO oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here experimental evolution of a Δ strain for ∼300 generations allowed to restore the activity of CcO oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the cytosolic AAA+ disaggregase Hsp104. Deletion or overexpression of also increased respiration of the Δ ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [] prion, which forms cytosolic amyloid aggregates of the Sup35 protein. Overall, our data demonstrate that cytosolic aggregation of a prion impairs the mitochondrial metabolism of cells defective for Cox12. These findings identify a new functional connection between cytosolic proteostasis and biogenesis of the mitochondrial respiratory chain.
细胞色素氧化酶（CcO）是线粒体呼吸链的关键酶，它维持真核细胞的生物能量。Cox12 是 CcO 氧化酶的一个外周亚基，是酶充分活性所必需的，但它的确切功能尚不清楚。在这里，对一个约 300 代的 Δ 菌株进行实验进化，使其能够恢复 CcO 氧化酶的活性。在一个种群中，增强的生物能量是由细胞质 AAA+解聚酶 Hsp104 的 A375V 突变引起的。缺失或过表达 也增加了 Δ 祖先菌株的呼吸作用。Hsp104 的这种有益作用与 [] 朊病毒的丧失有关，后者形成了 Sup35 蛋白的细胞质淀粉样聚集物。总的来说，我们的数据表明，朊病毒的细胞质聚集会损害 Cox12 缺陷细胞的线粒体代谢。这些发现确定了细胞质蛋白质稳态与线粒体呼吸链生物发生之间的新的功能联系。
