为了在营养匮乏的条件下增殖，肿瘤细胞对代谢通路进行复杂的重编程。然而由于细胞周期不同阶段的代谢需求不同，细胞还需进行代谢通路的及时切换。间期细胞既需要物质合成又要能量，而分裂期合成下降，能量需求增加。能量缺乏会造成细胞分裂阻滞，说明能量供应对有丝分裂的顺利完成十分重要，但是目前对分裂期能量代谢的调控知之甚少。前期通过活细胞观察，我们发现乳酸脱氢酶LDHB敲低对细胞分裂的影响与能量缺失一致，如果同时补充LDHB催化产物NADH可恢正常，暗示LDHB可能通过能量代谢调控细胞分裂进程。本课题中我们将利用分子探针等方法在活细胞中监控代谢物变化与细胞分裂进程的关联，进一步确认LDHB通过能量代谢促进分裂进程，发现其酶活变化规律和调控机理。还计划揭示能量供给调节有丝分裂的关键节点，探讨分裂期能量调控分子在肿瘤诊断和联合抗有丝分裂药物治疗中的应用。本课题将帮助我们从代谢角度去理解细胞分裂的精准调控机理。

In order to proliferate under nutrient-limiting conditions, cancer cells extensively reprogram their metabolic pathways. As the demands of metabolism are different in each cell cycle stage, cells also need instantly switch the metabolic pathway along the cell cycle progression. During mitosis, the biosynthesis is reduced while the demand of energy is increased. Energy deficiency in mitosis induces errors in chromosome alignment and delays in meta-anaphase transition, however, how energy metabolism is controlled in mitosis remains largely unclear. Our recent live cell work indicated that lactate dehydrogenase B (LDHB) is involved in energy supply in mitosis through catalyzing the generation of NADH, which promotes mitotic progression. In this study, we plan to validate the function of LDHB in energy production during mitosis in tumor cells. The enzymatic alteration of LDHB in mitosis and the underlying mechanism will be dissected. We also plan to study the key mitotic events that are associated with energy supply, and how these events delay the mitotic progression upon energy deficiency. The clinical implication of the energy metabolism during mitosis in diagnosis and combination chemotherapy will also be explored. This study may provide insights in the regulation of mitosis from the metabolic perspective.