State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
EMBO Rep. 2023 Dec 6;24(12):e57440. doi: 10.15252/embr.202357440. Epub 2023 Oct 27.
Embryogenesis is highly dependent on maternally loaded materials, particularly those used for energy production. Different environmental conditions and genetic backgrounds shape embryogenesis. The robustness of embryogenesis in response to extrinsic and intrinsic changes remains incompletely understood. By analyzing the levels of two major nutrients, glycogen and neutral lipids, we discovered stage-dependent usage of these two nutrients along with mitochondrial morphology changes during Caenorhabditis elegans embryogenesis. ATGL, the rate-limiting lipase in cellular lipolysis, is expressed and required in the hypodermis to regulate mitochondrial function and support embryogenesis. The embryonic lethality of atgl-1 mutants can be suppressed by reducing sinh-1/age-1-akt signaling, likely through modulating glucose metabolism to maintain sustainable glucose consumption. The embryonic lethality of atgl-1(xd314) is also affected by parental nutrition. Parental glucose and oleic acid supplements promote glycogen storage in atgl-1(xd314) embryos to compensate for the impaired lipolysis. The rescue by parental vitamin B12 supplement is likely through enhancing mitochondrial function in atgl-1 mutants. These findings reveal that metabolic plasticity contributes to the robustness of C. elegans embryogenesis.
胚胎发生高度依赖于母体加载的物质,特别是那些用于能量产生的物质。不同的环境条件和遗传背景会影响胚胎发生。胚胎发生对外部和内部变化的稳健性仍然不完全清楚。通过分析两种主要营养素——糖原和中性脂质的水平,我们发现,在秀丽隐杆线虫胚胎发生过程中,这两种营养素的使用以及线粒体形态变化与发育阶段有关。ATGL 是细胞脂肪分解的限速酶,在表皮层中表达并发挥作用,以调节线粒体功能并支持胚胎发生。atgl-1 突变体的胚胎致死性可以通过降低 sinh-1/age-1-akt 信号来抑制,这可能是通过调节葡萄糖代谢来维持可持续的葡萄糖消耗。atgl-1(xd314) 的胚胎致死性也受到亲本性营养的影响。亲本性糖和油酸补充剂促进 atgl-1(xd314) 胚胎中的糖原储存,以弥补脂肪分解的缺陷。亲本性维生素 B12 补充剂的挽救作用可能是通过增强 atgl-1 突变体中的线粒体功能。这些发现表明,代谢可塑性有助于秀丽隐杆线虫胚胎发生的稳健性。