Most mitochondrial proteins are encoded by DNA in the nucleus, which is transcribed into mRNA and then translated into proteins in the cytosol that are imported into mitochondria. Experiments show that mRNAs for many mitochondrial proteins are associated with the mitochondrial surface. This association is mediated by the mitochondrial targeting signal (MTS) region of these proteins. We aim to understand how translation kinetics and mitochondrial network geometry together regulate the degree of mRNA association with the mitochondrial surface. We simulate mRNA association with many three-dimensional experimentally-measured mitochondrial structures and with mRNA parameters corresponding to many different genes to investigate how these factors lead to diversity in mRNA association with mitochondria. While we recapitulate the experimental result that mitochondrial networks that occupy a higher fraction of the cell volume tend to have higher mitochondrial mRNA association, we also show that mitochondrial networks that occupy a similar fraction of the cell volume can have substantial variation in mRNA association. We find that mitochondria that are more evenly distributed throughout the cell volume have higher mRNA association via shorter diffusive search times for the mitochondrial surface. We reinforce earlier results to describe differences in mitochondrial mRNA association between genes, with longer mRNAs, higher initiation rates, and lower elongation rates leading to higher mitochondrial mRNA association. We find that the duration that an mRNA has at least one binding-competent MTS, enabling mitochondrial attachment, largely explains differences in mitochondrial association between genes. Overall, we find that a small ratio of diffusive search time (controlled by mitochondrial structure) to MTS exposure duration (determined by translation kinetics) leads to a high level of mRNA association with mitochondria. Our work thus explains how competition between search and translation kinetics regulates mRNA association with mitochondria.
Kim et al. (Sun,) studied this question.