Germline status and micronutrient availability regulate a somatic mitochondrial quality control pathway via short-chain fatty acid metabolism

种系状态和微量营养素可用性通过短链脂肪酸代谢调节体细胞线粒体质量控制途径

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作者:James P Held, Nadir H Dbouk, Adrianna M Strozak, Lantana K Grub, Hayeon Ryou, Samantha H Schaffner, Maulik R Patel

Abstract

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 Caenorhabditis elegans 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 (UPRmt). 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 UPRmt. 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.

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