Protein Sci. 2026 Apr;35(4):
e70545
Mitochondrial oxidative phosphorylation is the most efficient way of energy conversion for eukaryotic cells. It is executed by a series of high-molecular weight enzyme complexes in the inner mitochondrial membrane that were acquired during endosymbiosis at the root of eukaryotic evolution. Biogenesis of this machinery depends not only on nuclear gene expression and protein import, but also on an organelle-specific system to express a handful of proteins encoded in mitochondrial DNA. These two genetic systems cooperate for the biogenesis and maintenance of oxidative phosphorylation complexes. Here, we use the respiratory chain complex III as an example to highlight the complexities of this process. Specifically, we will describe the intricate mechanisms by which respiratory chain complexes are assembled, how the two genetic systems are coordinated and how biogenesis and function are physically separated within the inner mitochondrial membrane. To do so, we will primarily discuss findings from baker's yeast, where a wealth of recent data revealed exciting insights into these processes.
Keywords: OXPHOS; assembly; biogenesis; complex III; mitochondria; proteostasis; quality control; regulation; respiratory chain; translation