Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Sci Adv. 2024 Oct 4;10(40):eadp8351. doi: 10.1126/sciadv.adp8351.
Rapid elimination of paternal mitochondria following fertilization is a conserved event in most animals, but its physiological significance remains unclear. We find that modest delay of paternal mitochondrial elimination (PME) in embryos unexpectedly impairs mating and cognition of adult animals and alters their locomotion behaviors. Delayed PME causes decreased adenosine triphosphate (ATP) levels in early embryos, which lead to impaired physiological functions of adult animals through an energy-sensing pathway mediated by an adenosine monophosphate (AMP)-activated protein kinase, AAK-2, and a forkhead box class O (FOXO) transcription factor, DAF-16. Treatment of PME-delayed animals with MK-4, a subtype of vitamin K that can improve mitochondrial ATP production, restores ATP levels in early embryos, and rescues physiological defects of adult animals. Our results suggest that moderate PME delay during embryo development adversely affects crucial physiological functions in adults, which could be evolutionarily disadvantageous. These observations provide mechanistic explanations for the need to swiftly remove paternal mitochondria early during embryo development.
受精后父源线粒体的快速清除是大多数动物中保守的事件，但它的生理意义仍不清楚。我们发现，胚胎中父源线粒体清除（PME）的适度延迟出人意料地损害了成年动物的交配和认知能力，并改变了它们的运动行为。延迟的 PME 导致早期胚胎中三磷酸腺苷（ATP）水平降低，通过由单磷酸腺苷（AMP）激活的蛋白激酶 AAK-2 和叉头框 O 类（FOXO）转录因子 DAF-16 介导的能量感应途径，导致成年动物的生理功能受损。用 MK-4（维生素 K 的一种亚型，可改善线粒体 ATP 生成）治疗 PME 延迟的动物，可恢复早期胚胎中的 ATP 水平，并挽救成年动物的生理缺陷。我们的结果表明，胚胎发育过程中适度的 PME 延迟会对成年动物的关键生理功能产生不利影响，这在进化上可能是不利的。这些观察结果为需要在胚胎发育早期迅速清除父源线粒体提供了机制解释。
