Goncalves Jimmy, Wan Yufeng, Guo Xiaoyan, Rha Kyoungsun, LeBoeuf Brigitte, Zhang Liusuo, Estler Kerolayne, Garcia L René
Department of Biology, Texas A&M University, College Station, TX 77843, USA.
Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94158, USA.
iScience. 2020 Apr 24;23(4):100990. doi: 10.1016/j.isci.2020.100990. Epub 2020 Mar 19.
Dysregulated metabolism accelerates reduced decision-making and locomotor ability during aging. To identify mechanisms for delaying behavioral decline, we investigated how C. elegans males sustain their copulatory behavior during early to mid-adulthood. We found that in mid-aged males, gluco-/glyceroneogenesis, promoted by phosphoenolpyruvate carboxykinase (PEPCK), sustains competitive reproductive behavior. C. elegans' PEPCK paralogs, pck-1 and pck-2, increase in expression during the first 2 days of adulthood. Insufficient PEPCK expression correlates with reduced egl-2-encoded ether-a-go-go K+ channel expression and premature hyper-excitability of copulatory circuits. For copulation, pck-1 is required in neurons, whereas pck-2 is required in the epidermis. However, PCK-2 is more essential, because we found that epidermal PCK-2 likely supplements the copulation circuitry with fuel. We identified the subunit A of succinate dehydrogenase SDHA-1 as a potent modulator of PEPCK expression. We postulate that during mid-adulthood, reduction in mitochondrial physiology signals the upregulation of cytosolic PEPCK to sustain the male's energy demands.
新陈代谢失调会加速衰老过程中决策能力和运动能力的下降。为了确定延缓行为衰退的机制，我们研究了秀丽隐杆线虫雄性在成年早期到中期如何维持其交配行为。我们发现，在中年雄性线虫中，由磷酸烯醇丙酮酸羧激酶（PEPCK）促进的糖异生/甘油异生维持了竞争性生殖行为。秀丽隐杆线虫的PEPCK旁系同源基因pck-1和pck-2在成年后的前两天表达增加。PEPCK表达不足与egl-2编码的超极化激活环核苷酸门控钾离子通道（ether-a-go-go K+ channel）表达减少以及交配回路过早的过度兴奋相关。对于交配而言，pck-1在神经元中是必需的，而pck-2在表皮中是必需的。然而，PCK-2更为重要，因为我们发现表皮中的PCK-2可能为交配回路补充能量。我们确定琥珀酸脱氢酶SDHA-1的A亚基是PEPCK表达的有效调节因子。我们推测，在成年中期，线粒体生理功能的下降会促使胞质PEPCK上调，以维持雄性的能量需求。
