Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.
Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2220556120. doi: 10.1073/pnas.2220556120. Epub 2023 Sep 18.
Mammalian encodes a protein precursor of Irisin, which is important for exercise-dependent regulation of whole-body metabolism. In a genetic screen in , we identified (), which shows substantial protein homology to mouse and human , as a regulator of autophagy acting downstream of Atg1/Atg13. Physiologically, -deficient flies showed reduced exercise performance and defective cold resistance, which were rescued by exogenous expression of . Exercise training increased endurance in wild-type flies, but not in -deficient flies. Conversely, Idit is induced upon exercise training, and transgenic expression of in wild-type flies increased endurance to the level of exercise trained flies. Finally, deficiency prevented both exercise-induced increase in cardiac Atg8 and exercise-induced cardiac stress resistance, suggesting that cardiac autophagy may be an additional mechanism by which is involved in the adaptive response to exercise. Our work suggests an ancient role of an Iditarod/Irisin/FNDC5 family of proteins in autophagy, exercise physiology, and cold adaptation, conserved throughout metazoan species.
哺乳动物编码一种鸢尾素的蛋白前体，鸢尾素对于运动依赖的全身代谢调节很重要。在酵母的一个遗传筛选实验中，我们发现（），它与鼠和人源的有显著的蛋白同源性，作为自噬的调控因子，作用于 Atg1/Atg13 的下游。在生理条件下，-缺陷型果蝇表现出运动性能降低和耐寒性缺陷，而过表达则可以挽救这些缺陷。运动训练增加了野生型果蝇的耐力，而-缺陷型果蝇则不行。相反，Idit 在运动训练后被诱导表达，而在野生型果蝇中转基因表达 则将其耐力提高到了经过运动训练的果蝇的水平。最后，-缺陷型阻止了运动引起的心脏 Atg8 的增加和运动引起的心脏应激抵抗，这表明心脏自噬可能是 参与运动适应的另一个机制。我们的工作表明，Iditarod/鸢尾素/FNDC5 蛋白家族在自噬、运动生理学和冷适应方面具有古老的作用，在后生动物物种中保守。
