Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes
Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes
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DOI：
10.15252/embj.201490197
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发表时间：
2015-04-01
期刊：
影响因子：
11.4
通讯作者：
Martinou, Jean-Claude
中科院分区：
文献类型：
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作者：
Bender, Tom;Pena, Gabrielle;Martinou, Jean-Claude
在丙酮酸分支点，发酵和氧化代谢途径分叉。丙酮酸可以在哺乳动物细胞中转化为乳酸或在酵母中转化为乙醇，或者通过氧化磷酸化转运到线粒体中以促进ATP的产生。最近发现的线粒体丙酮酸载体（MPC），由MPC 1，MPC 2和MPC 3在酵母中编码，是丙酮酸摄取到细胞器所必需的。在这里，我们表明，虽然Mpc 1的表达是不依赖于碳源，Mpc 2和Mpc 3的表达是特定的发酵或呼吸条件下，分别。这就产生了两种可供选择的载体复合物，我们称之为MPCFERM和MPCOX。通过组成型表达的两个替代复合物在酵母中删除所有三个内源性基因，我们表明，MPCOX具有较高的运输活性比MPCFERM，这是依赖于Mpc 3的C-末端。我们建议，在酵母中的替代MPC亚基表达提供了一种适应细胞代谢的营养物质的可用性。
At the pyruvate branch point, the fermentative and oxidative metabolic routes diverge. Pyruvate can be transformed either into lactate in mammalian cells or into ethanol in yeast, or transported into mitochondria to fuel ATP production by oxidative phosphorylation. The recently discovered mitochondrial pyruvate carrier (MPC), encoded by MPC1, MPC2, and MPC3 in yeast, is required for uptake of pyruvate into the organelle. Here, we show that while expression of Mpc1 is not dependent on the carbon source, expression of Mpc2 and Mpc3 is specific to fermentative or respiratory conditions, respectively. This gives rise to two alternative carrier complexes that we have termed MPCFERM and MPCOX. By constitutively expressing the two alternative complexes in yeast deleted for all three endogenous genes, we show that MPCOX has a higher transport activity than MPCFERM, which is dependent on the C-terminus of Mpc3. We propose that the alternative MPC subunit expression in yeast provides a way of adapting cellular metabolism to the nutrient availability.