Held James P, Dbouk Nadir H, Strozak Adrianna M, Grub Lantana K, Ryou Hayeon, Schaffner Samantha H, Patel Maulik R
Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
bioRxiv. 2024 May 21:2024.05.20.594820. doi: 10.1101/2024.05.20.594820.
Reproductive status, such as pregnancy and menopause in women, profoundly influences metabolism of the body. Mitochondria likely orchestrate many of these metabolic changes. However, the influence of reproductive status on somatic mitochondria and the underlying mechanisms remain largely unexplored. We demonstrate that reproductive signals modulate mitochondria in the soma. We show that the germline acts via an RNA endonuclease, HOE-1, which despite its housekeeping role in tRNA maturation, selectively regulates the mitochondrial unfolded protein response (UPR). Mechanistically, we uncover a fatty acid metabolism pathway acting upstream of HOE-1 to convey germline status. Furthermore, we link vitamin B12's dietary intake to the germline's regulatory impact on HOE-1-driven UPR. Combined, our study uncovers a germline-somatic mitochondrial connection, reveals the underlying mechanism, and highlights the importance of micronutrients in modulating this connection. Our findings provide insights into the interplay between reproductive biology and metabolic regulation.
生殖状态，如女性的怀孕和更年期，会深刻影响身体的新陈代谢。线粒体可能在许多这些代谢变化中起协调作用。然而，生殖状态对体细胞线粒体的影响及其潜在机制在很大程度上仍未被探索。我们证明生殖信号可调节体细胞中的线粒体。我们表明生殖系通过一种RNA内切酶HOE-1发挥作用，尽管它在tRNA成熟中起管家作用，但它选择性地调节线粒体未折叠蛋白反应（UPR）。从机制上讲，我们发现了一条在HOE-1上游起作用以传达生殖系状态的脂肪酸代谢途径。此外，我们将维生素B12的饮食摄入量与生殖系对HOE-1驱动的UPR的调节作用联系起来。综合来看，我们的研究揭示了生殖系与体细胞线粒体之间的联系，揭示了潜在机制，并强调了微量营养素在调节这种联系中的重要性。我们的发现为生殖生物学和代谢调节之间的相互作用提供了见解。
