线粒体丙酮酸载体 1 (MPC1) 位于线粒体外膜上，介导丙酮酸从细胞质到线粒体的转运。众所周知，它还可以作为肿瘤抑制剂。六价铬（Cr（VI））污染因其高毒性和致癌性而构成全球挑战。本研究旨在探讨MPC1在Cr(VI)诱导致癌作用中的潜在机制。首先，Cr (VI) 处理降低了体外和体内 MPC1 的表达。 MPC1 的过表达抑制 Cr (VI) 诱导的 A549 细胞中的糖酵解和迁移。然后，高迁移率基团A2（HMGA2）蛋白通过与其启动子结合，强烈抑制MPC1的转录，并且HMGA2/MPC1轴在氧化磷酸化（OXPHOS）、糖酵解和细胞迁移中发挥重要作用。此外，内质网（ER）应激对HMGA2和MPC1之间的相互作用产生很大影响。最后，雷帕霉素 (mTOR) 的哺乳动物靶标被确定为介导 MPC1 调节的 OXPHOS、有氧糖酵解和细胞迁移。总的来说，我们的数据揭示了一种新的 HMGA2/MPC-1/mTOR 信号通路，通过促进从 OXPHOS 到有氧糖酵解的代谢重编程来促进细胞生长，这可能是癌症的潜在疗法。版权所有 © 2024。由 Elsevier B.V. 出版。

Mitochondrial Pyruvate Carrier 1 (MPC1) is localized on mitochondrial outer membrane to mediate the transport of pyruvate from cytosol to mitochondria. It is also well known to act as a tumor suppressor. Hexavalent chromium (Cr (VI)) contamination poses a global challenge due to its high toxicity and carcinogenesis. This research was intended to probe the potential mechanism of MPC1 in the effect of Cr (VI)-induced carcinogenesis. First, Cr (VI)-treatments decreased the expression of MPC1 in vitro and in vivo. Overexpression of MPC1 inhibited Cr (VI)-induced glycolysis and migration in A549 cells. Then, high mobility group A2 (HMGA2) protein strongly suppressed the transcription of MPC1 by binding to its promoter, and HMGA2/MPC1 axis played an important role in oxidative phosphorylation (OXPHOS), glycolysis and cell migration. Furthermore, endoplasmic reticulum (ER) stress made a great effect on the interaction between HMGA2 and MPC1. Finally, the mammalian target of the rapamycin (mTOR) was determined to mediate MPC1-regulated OXPHOS, aerobic glycolysis and cell migration. Collectively, our data revealed a novel HMGA2/MPC-1/mTOR signaling pathway to promote cell growth via facilitating the metabolism reprogramming from OXPHOS to aerobic glycolysis, which might be a potential therapy for cancers.Copyright © 2024. Published by Elsevier B.V.