Deregulated cell metabolism is one of the cancer hallmarks. Mitochondrial DNA mutations and enzyme defects, aberrant tumor suppressor or oncogenic activities cause mitochondrial dysfunction leading to deregulated cellular energetics. The tumor suppressor protein, p53 is a tetrameric transcription factor that in response to diverse genotoxic and non-genotoxic insults activates a plethora of target genes to preserve genome integrity. In the last two decades the discovery of cytoplasmic p53 localization focused intense research on its extra-nuclear functions. The ability of p53 to induce apoptosis acting directly at mitochondria and the related mechanisms of p53 localization and translocation in the cytoplasm have been investigated. A role of cytoplasmic p53 in autophagy, pentose phosphate pathway, fatty acid synthesis and oxidation, and drug response has been proposed. TP53 gene is mutated in more than half of human cancers. In parallel to loss of tumor suppressive functions, mutant p53 proteins often gain new tumorigenic activities (GOF, gain of function). It has been recently shown that mutant p53 proteins mediate metabolic changes thereby promoting cancer development and metastases. Here we review the contribution of either wild-type p53 or mutant p53 proteins to the fine-tuning of mitochondrial metabolism of both normal and cancer cells. Greater knowledge at the mechanistic level might provide insights to develop new cancer therapeutic approaches.

中文翻译：

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线粒体功能障碍中的野生型和突变型p53蛋白：在癌症疾病中的新兴见解。

细胞代谢失调是癌症的标志之一。线粒体DNA突变和酶缺陷，异常的肿瘤抑制物或致癌活性导致线粒体功能障碍，导致细胞能量学失调。肿瘤抑制蛋白p53是一种四聚体转录因子，可响应多种遗传毒性和非遗传毒性损伤而激活大量靶基因，以保持基因组完整性。在过去的二十年中，细胞质p53定位的发现将大量研究集中在其核外功能上。研究了p53诱导直接作用于线粒体的细胞凋亡的能力以及p53在细胞质中的定位和易位的相关机制。细胞质p53在自噬，磷酸戊糖途径，脂肪酸合成和氧化中的作用，并且已经提出了药物反应。TP53基因在一半以上的人类癌症中发生了突变。与丧失肿瘤抑制功能并行，突变的p53蛋白通常获得新的致瘤活性（GOF，功能获得）。最近已经表明，突变体p53蛋白介导代谢变化，从而促进癌症的发展和转移。在这里，我们回顾了野生型p53或突变型p53蛋白对正常细胞和癌细胞线粒体代谢的微调的贡献。机械方面的更多知识可能会为开发新的癌症治疗方法提供见识。最近已经表明，突变体p53蛋白介导代谢变化，从而促进癌症的发展和转移。在这里，我们回顾了野生型p53或突变型p53蛋白对正常细胞和癌细胞线粒体代谢的微调的贡献。在机理层面上的更多知识可能会为开发新的癌症治疗方法提供见识。最近已经表明，突变体p53蛋白介导代谢变化，从而促进癌症的发展和转移。在这里，我们回顾了野生型p53或突变型p53蛋白对正常细胞和癌细胞线粒体代谢的微调的贡献。机械方面的更多知识可能会为开发新的癌症治疗方法提供见识。