Department of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Cells. 2020 Jul 23;9(8):1764. doi: 10.3390/cells9081764.
Prostate cancer is one of the most prominent cancers diagnosed in males. Contrasting with other cancer types, glucose utilization is not increased in prostate carcinoma cells as they employ different metabolic adaptations involving mitochondria as a source of energy and intermediates required for rapid cell growth. In this regard, prostate cancer cells were associated with higher activity of mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), the key rate limiting component of the glycerophosphate shuttle, which connects mitochondrial and cytosolic processes and plays significant role in cellular bioenergetics. Our research focused on the role of mGPDH biogenesis and regulation in prostate cancer compared to healthy cells. We show that the 42 amino acid presequence is cleaved from N-terminus during mGPDH biogenesis. Only the processed form is part of the mGPDH dimer that is the prominent functional enzyme entity. We demonstrate that mGPDH overexpression enhances the wound healing ability in prostate cancer cells. As mGPDH is at the crossroad of glycolysis, lipogenesis and oxidative metabolism, regulation of its activity by intramitochondrial processing might represent rapid means of cellular metabolic adaptations.
前列腺癌是男性最常见的癌症之一。与其他癌症类型不同，前列腺癌细胞的葡萄糖利用率并没有增加，因为它们采用了不同的代谢适应方式，涉及线粒体作为能量来源和快速细胞生长所需的中间产物。在这方面，前列腺癌细胞与线粒体甘油-3-磷酸脱氢酶（mGPDH）的更高活性相关，mGPDH 是甘油磷酸穿梭的关键限速成分，连接线粒体和细胞质过程，并在细胞生物能量学中发挥重要作用。我们的研究重点是 mGPDH 生物发生和调节在前列腺癌与健康细胞中的作用。我们表明，在 mGPDH 生物发生过程中，42 个氨基酸的前导序列从 N 端被切割。只有经过加工的形式才是 mGPDH 二聚体的一部分，mGPDH 二聚体是主要的功能性酶实体。我们证明 mGPDH 的过表达增强了前列腺癌细胞的伤口愈合能力。由于 mGPDH 处于糖酵解、脂肪生成和氧化代谢的交汇点，其活性的线粒体内部加工可能代表了细胞代谢适应的快速手段。
