Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form (NADP) are vital for cell function in all organisms and form cofactors to a host of enzymes in catabolic and anabolic processes. NAD(P) transhydrogenases (NTHs) catalyse hydride ion transfer between NAD(H) and NADP(H). Membrane-bound NTH isoforms reside in the cytoplasmic membrane of bacteria, and the inner membrane of mitochondria in metazoans, where they generate NADPH. Here, we show that malaria parasites encode a single membrane-bound NTH that localises to the crystalloid, an organelle required for sporozoite transmission from mosquitos to vertebrates. We demonstrate that NTH has an essential structural role in crystalloid biogenesis, whilst its enzymatic activity is required for sporozoite development. This pinpoints an essential function in sporogony to the activity of a single crystalloid protein. Its additional presence in the apicoplast of sporozoites identifies NTH as a likely supplier of NADPH for this organelle during liver infection. Our findings reveal that Plasmodium species have co-opted NTH to a variety of non-mitochondrial organelles to provide a critical source of NADPH reducing power.

中文翻译：

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NAD(P) 转氢酶在疟疾寄生虫传播中具有重要的非线粒体功能。

烟酰胺腺嘌呤二核苷酸 (NAD) 及其磷酸化形式 (NADP) 对所有生物体的细胞功能至关重要，并在分解代谢和合成代谢过程中形成许多酶的辅助因子。NAD(P) 转氢酶 (NTH) 催化 NAD(H) 和 NADP(H) 之间的氢阴离子转移。膜结合的 NTH 同种型存在于细菌的细胞质膜和后生动物线粒体的内膜中，它们在那里产生 NADPH。在这里，我们表明疟原虫编码一个单一的膜结合 NTH，该 NTH 定位于晶体，这是从蚊子到脊椎动物的子孢子传播所需的细胞器。我们证明 NTH 在晶体生物发生中具有重要的结构作用，而其酶活性是子孢子发育所必需的。这将孢子发生中的一个基本功能确定为单个晶体蛋白的活性。它在子孢子的顶端质体中的额外存在将 NTH 确定为肝脏感染期间该细胞器的 NADPH 的可能供应者。我们的研究结果表明，疟原虫物种已将 NTH 加入到各种非线粒体细胞器中，以提供 NADPH 还原能力的关键来源。