TY - JOUR TI - Homeostatic control of an iron repressor in a GI tract resident AU - Wang, Yuanyuan AU - Mao, Yinhe AU - Chen, Xiaoqing AU - Huang, Xinhuang AU - Jiang, Zhongyi AU - Yang, Kaiyan AU - Tian, Lixing AU - Jiang, Tong AU - Zou, Yun AU - Ma, Xiaoyuan AU - Xu, Chaoyue AU - Zhou, Zili AU - Wu, Xianwei AU - Pan, Lei AU - Liang, Huaping AU - Zhong, Lin AU - Chen, Changbin A2 - Rokas, Antonis A2 - Garrett, Wendy S A2 - Tsai, Yu-Huan A2 - Gourlay, Campbell Gourlay A2 - Brunke, Sascha VL - 12 PY - 2023 DA - 2023/05/25 SP - e86075 C1 - eLife 2023;12:e86075 DO - 10.7554/eLife.86075 UR - https://doi.org/10.7554/eLife.86075 AB - The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus Candida albicans for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of C. albicans to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism. KW - Candida albicans KW - iron KW - Hap43 KW - oxidative damage KW - cellular detoxification JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -