Mitochondrial regulation in cardiovascular and cancer biology

我们已经证明，P53通过其对线粒体呼吸的正向调节来平衡氧化磷酸化和糖酵解产生的能量，并促进有氧代谢。P53基因缺失的小鼠是早期肿瘤发生的模型，在有氧运动能力方面表现出严重的缺陷。值得注意的是，在小鼠模型中，肿瘤抑制基因促进了运动能力，这与人类流行病学观察到的运动能力与癌症发病率之间存在强烈的负相关关系是平行的。我们认为这两个不同的观察结果可能在抑制肿瘤方面具有共同的机制，因此，我们正在使用体外和体内模型研究P53对线粒体功能的调节。重要的是，我们正在研究Li-Fraumeni综合征患者的心血管和代谢功能，Li-Fraumeni综合征是一种由p53基因胚系突变引起的早癌综合征。这项研究的一个目标是获得基本的见解，这些见解可能有助于开发预防癌症和改善心血管健康的新策略。

We have shown that p53 balances the energy generated by oxidative phosphorylation and glycolysis and promotes aerobic metabolism through it positive regulation of mitochondrial respiration. p53 null mice, a model of premature tumorigenesis, display profound deficiencies in aerobic exercise capacity. Remarkably, the promotion of exercise capacity by a tumor suppressor gene in a mouse model parallels the human epidemiologic observation of a strong inverse relationship between exercise capacity and cancer incidence. We believe these two disparate observations may share a common mechanism in tumor suppression, therefore, we are investigating the regulation of mitochondrial function by p53 using in vitro and in vivo models. Importantly, we are studying cardiovascular and metabolic functions in individuals with Li-Fraumeni syndrome, a premature cancer syndrome caused by germline mutations in the p53 gene. A goal of this research is to derive basic insights that may assist in the development of new strategies for preventing cancer and improving cardiovascular fitness.