Sellem Carole H, di Rago Jean-Paul, Lasserre Jean-Paul, Ackerman Sharon H, Sainsard-Chanet Annie
Institute for Integrative Biology of the Cell (I2BC), CEA-CNRS-Université Paris-Sud, Gif sur Yvette, France.
CNRS, Institut de Biochimie et Génétique Cellulaires, UMR 5095, Bordeaux, France.
PLoS Genet. 2016 Jul 21;12(7):e1006161. doi: 10.1371/journal.pgen.1006161. eCollection 2016 Jul.
Most of the ATP in living cells is produced by an F-type ATP synthase. This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate. Proton movements across the membrane domain (FO) of the ATP synthase drive the rotation of a ring of 8-15 c-subunits, which induces conformational changes in the catalytic part (F1) of the enzyme that ultimately promote ATP synthesis. Two paralogous nuclear genes, called Atp9-5 and Atp9-7, encode structurally different c-subunits in the filamentous fungus Podospora anserina. We have in this study identified differences in the expression pattern for the two genes that correlate with the mitotic activity of cells in vegetative mycelia: Atp9-7 is transcriptionally active in non-proliferating (stationary) cells while Atp9-5 is expressed in the cells at the extremity (apex) of filaments that divide and are responsible for mycelium growth. When active, the Atp9-5 gene sustains a much higher rate of c-subunit synthesis than Atp9-7. We further show that the ATP9-7 and ATP9-5 proteins have antagonist effects on the longevity of P. anserina. Finally, we provide evidence that the ATP9-5 protein sustains a higher rate of mitochondrial ATP synthesis and yield in ATP molecules per electron transferred to oxygen than the c-subunit encoded by Atp9-7. These findings reveal that the c-subunit genes play a key role in the modulation of ATP synthase production and activity along the life cycle of P. anserina. Such a degree of sophistication for regulating aerobic energy metabolism has not been described before.
活细胞中的大多数ATP是由F型ATP合酶产生的。这种酶利用跨膜电化学质子梯度的能量，将ADP和无机磷酸合成为ATP。质子跨ATP合酶膜结构域（FO）的移动驱动8 - 15个c亚基组成的环的旋转，这会诱导该酶催化部分（F1）的构象变化，最终促进ATP的合成。在丝状真菌粗糙脉孢菌中，两个同源核基因Atp9-5和Atp9-7编码结构不同的c亚基。在本研究中，我们发现这两个基因的表达模式存在差异，这些差异与营养菌丝体细胞的有丝分裂活性相关：Atp9-7在非增殖（静止）细胞中具有转录活性，而Atp9-5在负责菌丝体生长的丝状顶端分裂细胞中表达。当Atp9-5基因活跃时，其c亚基的合成速率比Atp9-7高得多。我们进一步表明，ATP9-7和ATP9-5蛋白对粗糙脉孢菌的寿命具有拮抗作用。最后，我们提供证据表明，与Atp9-7编码的c亚基相比，ATP9-5蛋白维持更高的线粒体ATP合成速率，并且每转移到氧的电子产生的ATP分子产量更高。这些发现表明，c亚基基因在粗糙脉孢菌生命周期中对ATP合酶的产生和活性的调节中起关键作用。这种调节有氧能量代谢的复杂程度以前尚未有过描述。
