Fungi lack the entire animal core apoptotic machinery. Nevertheless, regulated cell death with apoptotic markers occurs in multicellular as well as in unicellular fungi and is essential for proper fungal development and stress adaptation. The discrepancy between appearance of an apoptotic-like regulated cell death (RCD) in the absence of core apoptotic machinery is further complicated by the fact that heterologous expression of animal apoptotic genes in fungi affects fungal RCD. Here we describe the role of BcMcl, a methyl isocitrate lyase from the plant pathogenic fungus Botrytis cinerea, in succinate metabolism, and the connection of succinate with stress responses and cell death. Over expression of bcmcl resulted in elevated tolerance to oxidative stress and reduced levels of RCD, which were associated with accumulation of elevated levels of succinate. Deletion of bcmcl had almost no effect on fungal development or stress sensitivity, and succinate levels were unchanged in the deletion strain. Gene expression experiments showed co-regulation of bcmcl and bcicl (isocitrate lyase); expression of the bcicl gene was enhanced in bcmcl deletion and suppressed in bcmcl over expression strains. External addition of succinate reproduced the phenotypes of the bcmcl over expression strains, including developmental defects, reduced virulence, and improved oxidative stress tolerance. Collectively, our results implicate mitochondria metabolic pathways, and in particular succinate metabolism, in regulation of fungal stress tolerance, and highlight the role of this onco-metabolite as potential mediator of fungal RCD.

真菌缺乏整个动物核心的凋亡机制。尽管如此，在多细胞和单细胞真菌中都发生了凋亡标记物调节的细胞死亡，这对于真菌的正常发育和应激适应至关重要。由于真菌中动物凋亡基因的异源表达影响真菌 RCD，在缺乏核心凋亡机制的情况下，凋亡样调节细胞死亡 (RCD) 的出现之间的差异进一步复杂化。在这里，我们描述了 BcMcl（一种来自植物病原真菌灰葡萄孢菌的甲基异柠檬酸裂解酶）在琥珀酸代谢中的作用，以及琥珀酸与应激反应和细胞死亡的联系。bcmcl 的过度表达导致对氧化应激的耐受性提高和 RCD 水平降低，这与琥珀酸水平升高的积累有关。bcmcl 的缺失对真菌发育或应激敏感性几乎没有影响，并且缺失菌株中的琥珀酸水平没有变化。基因表达实验显示bcmcl和bcicl（异柠檬酸裂解酶）共同调控；bcmcl基因的表达在bcmcl缺失中增强，在bcmcl过表达菌株中被抑制。琥珀酸的外部添加再现了bcmcl的表型过表达菌株，包括发育缺陷、毒力降低和氧化应激耐受性提高。总的来说，我们的结果表明线粒体代谢途径，特别是琥珀酸代谢，在调节真菌胁迫耐受性中，并强调了这种肿瘤代谢物作为真菌 RCD 潜在介质的作用。