eIF5A controls mitoprotein import by relieving ribosome stalling at the TIM50 translocase mRNA.

The efficient import of nuclear-encoded proteins into mitochondria is crucial for proper mitochondrial function. The conserved translation factor eIF5A is primarily known as an elongation factor which binds ribosomes to alleviate ribosome stalling at sequences encoding polyprolines or combinations of proline with glycine and charged amino acids. eIF5A is known to impact the mitochondrial function across a variety of species although the precise molecular mechanism underlying this impact remains unclear. We found that depletion of eIF5A in yeast drives reduced translation and levels of TCA cycle and oxidative phosphorylation proteins. We further found that loss of eIF5A leads to the accumulation of mitoprotein precursors in the cytosol as well as to the induction of a mitochondrial import stress response. Here we identify an essential polyproline-containing protein as a direct eIF5A target for translation: the mitochondrial inner membrane protein Tim50, which is the receptor subunit of the TIM23 translocase complex. We show how eIF5A directly controls mitochondrial protein import through the alleviation of ribosome stalling along TIM50 mRNA at the mitochondrial surface. Removal of the polyprolines from Tim50 rescues the mitochondrial import stress response, as well as the translation of oxidative phosphorylation reporter genes in an eIF5A loss of function. Overall, our findings elucidate how eIF5A impacts the mitochondrial function by reducing ribosome stalling and facilitating protein translation, thereby positively impacting the mitochondrial import process.

Efficacy of Posterior Tibial Nerve Stimulation in the Treatment of Fecal Incontinence: A Systematic Review.

Fecal incontinence is a condition that carries high social stigmatization and a determining factor in the quality of life of the person who suffers from it. Its etiology is multifactorial and treatment includes surgical and conservative measures, including stimulation of the posterior tibial nerve. The aim of this review is to determine whether posterior tibial nerve stimulation (PTNS) is more effective than other treatments in reducing episodes of fecal incontinence in adults. A systematic review of randomized clinical trials that analyzed different approaches and comparisons with other treatments in adults without neurological or metabolic diseases was carried out, analyzing, fundamentally, the reduction of episodes of fecal incontinence. In general, a reduction in fecal incontinence episodes is observed in the experimental groups compared with the control groups, although these differences are not significant in most studies. The results regarding the effectiveness of PTNS in reducing episodes of fecal incontinence compared to other treatments are not entirely conclusive, although benefits are observed regarding the stimulation of sacral roots. More well-designed studies with a long-term follow-up of the results are needed so that the recommendation of this treatment can be generalized.