Mitochondrial ubiquinone-mediated longevity is marked by reduced cytoplasmic protein translation

Abstract

Mutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan of C. elegans. We demonstrate here that this life extension is linked to the repression of cytoplasmic protein translation. Clk-1 mutations inhibit polyribosome formation similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs in clk-1 mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TAF-4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates the clk-1 inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein translation in eukaryotic lifespan extension, and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TAF-4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.