In insect, pyruvate is generally the predominant oxidative substrate for mitochondria. This metabolite is transported inside mitochondria via the mitochondrial pyruvate carrier (MPC), but whether and how this transporter controls mitochondrial oxidative capacities in insects is still relatively unknown. Here, we characterize the importance of pyruvate transport as a metabolic control point for mitochondrial substrate oxidation in two genotypes of an insect model, Drosophila melanogaster, differently expressing MPC1, an essential protein for the MPC function. We evaluated the kinetics of pyruvate oxidation, mitochondrial oxygen consumption, metabolic profile, activities of metabolic enzymes, and climbing abilities of wild-type (WT) flies and flies harboring a deficiency in MPC1 (MPC1^def). We hypothesized that MPC1 deficiency would cause a metabolic reprogramming that would favor the oxidation of alternative substrates. Our results show that the MPC1^def flies display significantly reduced climbing capacity, pyruvate-induced oxygen consumption, and enzymatic activities of pyruvate kinase, alanine aminotransferase, and citrate synthase. Moreover, increased proline oxidation capacity was detected in MPC1^def flies, which was associated with generally lower levels of several metabolites, and particularly those involved in amino acid catabolism such as ornithine, citrulline, and arginosuccinate. This study therefore reveals the flexibility of mitochondrial substrate oxidation allowing Drosophila to maintain cellular homeostasis.

中文翻译：

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果蝇的线粒体丙酮酸携带者缺乏症的代谢特征和后果。

在昆虫中，丙酮酸通常是线粒体的主要氧化底物。该代谢产物通过线粒体丙酮酸载体（MPC）转运到线粒体内，但是这种转运蛋白是否以及如何控制昆虫中的线粒体氧化能力仍然相对未知。在这里，我们表征了丙酮酸转运作为昆虫模型的两种基因型果蝇（Drosophila melanogaster）的两种基因型中线粒体底物氧化的代谢控制点的重要性，其不同表达MPC1，这是MPC功能的必需蛋白。我们评估了丙酮酸氧化动力学，线粒体耗氧量，代谢谱，代谢酶活性以及野生型（WT）蝇和MPC1（MPC1 ^def缺乏症）蝇的爬升能力。）。我们假设MPC1缺乏会导致代谢重编程，从而有利于其他底物的氧化。我们的结果表明，该MPC1 ^DEF蝇显示显著降低爬坡能力，丙酮酸诱导的耗氧量，丙酮酸激酶，丙氨酸氨基转移酶的酶活性，和柠檬酸合酶。此外，在MPC1检测增加脯氨酸的氧化能力^DEF苍蝇，将其用通常较低水平的几种代谢物相关联，并且特别是参与氨基酸分解代谢如鸟氨酸，瓜氨酸，精氨琥珀酸和。因此，这项研究揭示了线粒体底物氧化的灵活性，使果蝇能够维持细胞稳态。