Iron-responsive transcription factor SreA regulates calcium homeostasis independently of calcineurin–Crz1 pathway in <i>Fusarium graminearum</i>

ABSTRACT Calcium is an abundant intracellular ion that is intricately involved in various cellular processes. The precise regulation of calcium homeostasis is critical for fungal physiology. In fungi, calcium signaling is primarily mediated by the calmodulin–calcineurin pathway, with the transcription factor Crz1 acting as a key downstream regulator of calcium homeostasis. However, other transcription factors that contribute to calcium homeostasis in Fusarium graminearum are yet to be systematically identified. Here, we screened 675 transcription factor deletion mutants of F. graminearum under calcium stress and identified eight mutants, including crz1 and sreA . We found that SreA, a known iron homeostasis regulator, is required for calcium stress tolerance, separate from its role in iron homeostasis. Furthermore, SreA functions independently of the calcineurin–Crz1 pathway, and deletion of SREA alters cytosolic Ca 2+ dynamics following calcium stimulation. Our findings highlight a previously unrecognized role of SreA in fungal calcium homeostasis and suggest that SreA contributes to calcium stress response by maintaining appropriate cytosolic Ca 2+ signaling in F. graminearum . IMPORTANCE Calcium regulation is vital for the survival and pathogenicity of fungi. While the transcription factor Crz1 is widely recognized as the main regulator of calcium homeostasis, this study reveals that another transcription factor, SreA, plays a critical and previously unrecognized role in Fusarium graminearum . Although SreA is a well-established regulator of iron homeostasis, it also plays a critical role in calcium stress tolerance. This function is independent of both iron homeostasis and the canonical calcineurin–Crz1 pathway. Together, these findings broaden our understanding of the transcriptional regulators involved in fungal calcium homeostasis.