Dietary Piperine is Transferred into the Milk of Nursing Mothers

Introduction The diet of breastfeeding mothers could bring nurslings into contact with flavor compounds putatively contributing to early sensory programming of the infant. The study investigates whether tastants from a customary curry dish consumed by mothers are detectable in their milk afterwards and can be perceived by the infant. Methods and Results Sensory evaluation identifies pungency as the dominating taste impression of the curry dish. Its ingredients of chili, pepper, and ginger suggest the flavor compounds capsaicin, piperine, and 6‐gingerol as analytical targets. Breastfeeding mothers are recruited for an intervention trial involving the consumption of the curry dish and subsequent collection of milk samples for flavor compound analysis. Targeted and untargeted mass spectrometric (MS)‐ investigations identify exclusively piperine as an intervention‐derived compound in human milk. However, concentrations are below the human taste threshold. Conclusion Piperine from pepper‐containing foods transfers into the mother's milk within 1 h and is delivered to the nursling. Concentrations of 50 and 200 nM of piperine are 70–350 times below the human taste threshold, but TRPV1 (Transient Receptor Potential Vanilloid‐1 ion channel) desensitization through frequent exposure to sub‐taste‐threshold concentrations could contribute to an increased tolerance at a later age

The α-Helical Structure of Prodomains Promotes Translocation of Intrinsically Disordered Neuropeptide Hormones into the Endoplasmic Reticulum

Different neuropeptide hormones, which are either too small to adopt a stable conformation or are predicted to be intrinsically disordered, are synthesized as larger precursors containing a prodomain in addition to an N-terminal signal peptide. We analyzed the biogenesis of three unstructured neuropeptide hormones and observed that translocation of these precursors into the lumen of the endoplasmic reticulum (ER) is critically dependent on the presence of the prodomain. The hormone domains could be deleted from the precursors without interfering with ER import and secretion, whereas constructs lacking the prodomain remained in the cytosol. Domain-swapping experiments revealed that the activity of the prodomains to promote productive ER import resides in their ability to adopt an α-helical structure. Removal of the prodomain from the precursor did not interfere with co-translational targeting of the nascent chain to the Sec61 translocon but with its subsequent productive translocation into the ER lumen. Our study reveals a novel function of prodomains to enable import of small or intrinsically disordered secretory proteins into the ER based on their ability to adopt an α-helical conformation

Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria

Protein targeting to specified cellular compartments is essential to maintain cell function and homeostasis. In eukaryotic cells, two major pathways rely on N-terminal signal peptides to target proteins to either the endoplasmic reticulum (ER) or mitochondria. In this study, we show that the ER signal peptides of the prion protein-like protein shadoo, the neuropeptide hormone somatostatin and the amyloid precursor protein have the property to mediate alternative targeting to mitochondria. Remarkably, the targeting direction of these signal peptides is determined by structural elements within the nascent chain. Each of the identified signal peptides promotes efficient ER import of nascent chains containing alpha-helical domains, but targets unstructured polypeptides to mitochondria. Moreover, we observed that mitochondrial targeting by the ER signal peptides correlates inversely with ER import efficiency. When ER import is compromised, targeting to mitochondria is enhanced, whereas improving ER import efficiency decreases mitochondrial targeting. In conclusion, our study reveals a novel mechanism of dual targeting to either the ER or mitochondria that is mediated by structural features within the nascent chain