Retrograde regulation due to mitochondrial dysfunction may be an important mechanism for carcinogenesis
Retrograde regulation due to mitochondrial dysfunction may be an important mechanism for carcinogenesis
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DOI：
10.1016/j.mehy.2005.03.022
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Erol, A
中科院分区：
文献类型：
--
作者：
Erol, A
线粒体功能障碍在肿瘤发生中具有至关重要的作用。由于多种原因，它可能导致电子传递链的不足，从而激活一系列胞质蛋白。这些蛋白质被转运到细胞核并促进基因的激活，导致细胞内多种代谢、调节、信号转导和应激相关途径。逆行调节是线粒体信号传导的总称，广义上被定义为细胞对线粒体功能状态改变的反应。这个信号通路是由线粒体触发的。功能障碍逆行反应不是一个简单的开关，而是以连续的方式响应细胞不断变化的代谢需求。线粒体和细胞核之间的通讯对于各种细胞过程如碳水化合物和氮代谢、细胞周期和增殖以及细胞生长和形态发生是重要的。作为逆向调节的结果，细胞，实际上是多细胞生物体的一个组成部分，转变为单细胞的生活方式，并开始独立于系统结构的发育过程。这种转化的细胞有效地运行代谢调节，以利用能量库，主要是多细胞生物体的脂肪组织。其中最重要的是积极利用葡萄糖酸循环，恶性细胞通过该循环从脂肪中提供葡萄糖。持续作用的糖酵解和脂肪异生、脂肪酸氧化和从头脂肪生成构成无效循环。这反过来又会导致恶病质维持有机体在不断的负能量平衡。线粒体到细胞核的应激信号传导激活了一些与肿瘤进展和肿瘤细胞转移有关的基因。逆行调节也使细胞对凋亡更具抵抗力。现在越来越清楚哪些基因控制着人体细胞中的逆行反应。最有可能的是，MYC是这种反应所必需的转录因子之一。(c)2005年由Elsevier Ltd.出版
Mitochondrial dysfunction has crucial importance in carcinogenesis. Due to several reasons, it may lead to insufficiency in the electron transport chain, which activates a series of cytosolic proteins. These proteins are transported to the nucleus and promote the activation of genes leading to intracellular diverse metabolic, regulatory, signatization and stress-related pathways. Retrograde regulation is the general term for mitochondrial signaling, and is broadly defined as cellular responses to alterations in functional state of mitochondria. This signaling pathway is triggered by mitochondrial. dysfunction. The retrograde response is not a simple On-Off switch, but rather it responds in a continuous manner to the changing metabolic needs of the cell. Communication between mitochondria and the nucleus is important for a variety of cellular processes such as carbohydrate and nitrogen metabolism, cell cycle and proliferation, and cell growth and morphogenesis. As a result of retrograde regulation, the cell, actually a component of the multicellular organism, transforms to a unicellular lifestyle and initiates a developing course, independent of the systemic structure. This transformed cell runs metabolic regulations effectively in order to utilize at[ energy depots, mainly the adipose tissue of the multicellular organism. The most important one is the active utilization of gtyoxylate cycle, through which the malign cells supply glucose from fats. Continuously acting glycolysis and gluconeogenesis, fatty acid oxidation and de novo lipogenesis constitute futile cycles. This in turn causes cachexia by maintaining the organism in constant negative energy balance. Mitochondria-to-nucleus stress signaling activates some of the genes implicated in tumor progression and tumor cell metastasis. Retrograde regulation also renders the cell more resistant to apoptosis. It is becoming clearer which genes control the retrograde response in human cells. Most probably, MYC is one of the transcription factors necessary for this response. (c) 2005 Published by Elsevier Ltd.