Molecular Wiring of a Mitochondrial Translational Feedback Loop

• Published in: Molecular cell Vol. 77; no. 4; pp. 887 - 900.e5
• Main Authors: Salvatori, Roger, Kehrein, Kirsten, Singh, Abeer Prakash, Aftab, Wasim, Möller-Hergt, Braulio Vargas, Forne, Ignasi, Imhof, Axel, Ott, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2020
• Subjects: Biochemistry; biokemi; Mitochondrial biogenesis; mitochondrial gene expression; mitochondrial ribosome; mitoribosome interactors; respiratory chain assembly; ribosomal tunnel exit; translation activation; translation regulation; mitoribosome interactors; Mitochondrial biogenesis; mitochondrial gene expression; translation regulation; ribosomal tunnel exit; translation activation; mitochondrial ribosome; respiratory chain assembly
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2019.11.019

The mitochondrial oxidative phosphorylation system comprises complexes assembled from subunits derived from mitochondrial and nuclear gene expression. Both genetic systems are coordinated by feedback loops, which control the synthesis of specific mitochondrial encoded subunits. Here, we studied how this occurs in the case of cytochrome b, a key subunit of mitochondrial complex III. Our data suggest the presence of a molecular rheostat consisting of two translational activators, Cbp3-Cbp6 and Cbs1, which operates at the mitoribosomal tunnel exit to connect translational output with assembly efficiency. When Cbp3-Cbp6 is engaged in assembly of cytochrome b, Cbs1 binds to the tunnel exit to sequester the cytochrome b-encoding mRNA, repressing its translation. After mediating complex III assembly, binding of Cbp3-Cbp6 to the tunnel exit replaces Cbs1 and the bound mRNA to permit cytochrome b synthesis. Collectively, the data indicate the molecular wiring of a feedback loop to regulate synthesis of a mitochondrial encoded protein. [Display omitted] •Translational feedback regulation in mitochondria involves a molecular rheostat•Alternate binding of two translational activators to the ribosomal tunnel exit•Ribosomal binding of Cbs1 sequesters COB mRNA to repress translation•Cbp3-Cbp6 liberated during assembly replaces Cbs1 for translational activation Salvatori et al. identify a pathway by which a feedback loop operates to regulate mitochondrial translation of a specific mRNA. Alternating binding of two translational activators to the mitoribosomal tunnel exit causes either activation or repression of cytochrome b synthesis, depending on the efficiency of respiratory chain assembly.