Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in various foods and mammalian tissues, has received an increasing amount of attention because of a number of health benefits that can be attributed to its ability to enhance mitochondrial biogenesis. However, its underlying molecular mechanism remains incompletely understood. We have now established that the exposure of mouse NIH/3T3 fibroblasts to a physiologically relevant concentration of PQQ significantly stimulates mitochondrial biogenesis. The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD⁺-dependent protein deacetylase sirtuin 1 (SIRT1). Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD⁺ levels, but not the total NAD⁺ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD⁺ formation.

中文翻译：

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吡咯并喹啉醌是一种具有氧化还原活性的邻醌，可通过激活SIRT1 /PGC-1α信号通路来刺激线粒体生物发生。

吡咯喹啉醌（PQQ），氧化还原活性Ø -quinone各种食品和哺乳动物组织中发现，已收到，因为许多健康的好处，可以归因于它，以增强线粒体生物合成能力的关注越来越量。但是，其潜在的分子机制仍不完全了解。现在我们已经确定，将小鼠NIH / 3T3成纤维细胞暴露于生理相关浓度的PQQ会显着刺激线粒体的生物发生。NIH / 3T3细胞在10–100 nM PQQ中暴露48 h导致线粒体染色，线粒体DNA含量和线粒体编码的细胞色素c含量增加氧化酶亚基1（MTCO1）蛋白。此外，我们观察到PQQ处理诱导了过氧化物酶体增殖物激活的受体-γ-共激活剂1α（PGC-1α）的去乙酰化，并促进了其核易位和靶基因表达，但不影响其蛋白质水平，暗示NAD ^+的活性增加。依赖性蛋白脱乙酰基酶Sirtuin 1（SIRT1）。实际上，用SIRT1选择性抑制剂EX-527进行的治疗阻碍了PQQ刺激PGC-1α介导的线粒体生物发生的能力。我们还发现，PQQ治疗可引起细胞NAD ⁺浓度的浓度依赖性增加，但不会引起总NAD ⁺浓度的增加。和NADH水平。我们的结果表明，PQQ诱导的线粒体生物发生可归因于SIRT1 /PGC-1α信号通路的激活，其通过增强细胞NAD ^+的形成来实现。