Pyrroloquinoline quinone (PQQ), an aromatic tricyclic o-quinone, was identified initially as a redox cofactor for bacterial dehydrogenases. Although PQQ is not biosynthesized in mammals, trace amounts of PQQ have been found in human and rat tissues because of its wide distribution in dietary sources. Importantly, nutritional studies in rodents have revealed that PQQ deficiency exhibits diverse systemic responses, including growth impairment, immune dysfunction, and abnormal reproductive performance. Although PQQ is not currently classified as a vitamin, PQQ has been implicated as an important nutrient in mammals. In recent years, PQQ has been receiving much attention owing to its physiological importance and pharmacological effects. In this article, we review the potential health benefits of PQQ with a focus on its growth-promoting activity, anti-diabetic effect, anti-oxidative action, and neuroprotective function. Additionally, we provide an update of its basic pharmacokinetics and safety information in oral ingestion.

Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase and dual oxidase (DUOX) system, which could extend lifespan in Caenorhabditis elegans. A redox co-factor, pyrroloquinoline quinone (PQQ), activates the C. elegans DUOX protein BLI-3 to produce the ROS H 2 O 2 at the plasma membrane, which is subsequently degraded by peroxidase (MLT-7), eventually ensuring adequate levels of ROS. These ROS signals are transduced mainly by the oxidative stress transcriptional factors SKN-1 (Nrf2 or NFE2L2 in mammals) and JUN-1, and partially by DAF-16 (a FOXO protein homolog). Cell biology experiments demonstrated a similarity between the mechanisms of PQQ-induced activation of human DUOX1 and DUOX2 and that of C. elegans BLI-3, suggesting that DUOXs are potential targets of intervention for lifespan extension. We propose that low levels of ROS, fine-tuned by the peroxidase and dual oxidase system at the plasma membrane, act as second messengers to extend lifespan by the effect of hormesis.

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.

Charged water droplets from an electrospray device can generate a transient hole in cell membranes for DNA transport into a living cell. The number of cells containing DNA encoded with green fluorescent protein (GFP) increases with an increase in applied voltage. The technique can be applied to gene transfection to eukaryotic cells, tissues, and prokaryotic cells.

Pyrroloquinoline quinone (PQQ) is contained in fruits and vegetables and in human breast milk. It has been reported that PQQ has high reactivity and changes to an imidazole structure (imidazole pyrroloquinoline) by a reaction with an amino acid at a high ratio in nature. A comparative study was conducted to clarify physiological effects including neuroprotective effects, growth-promoting effect, antioxidative effects and a stimulatory effect on mitochondriogensis of PQQ and imidazole pyrroloquinoline (IPQ) using a human neuroblastoma cell line and a hepatocellular carcinoma cell line. We also compared the expression levels of human cytochrome c oxidase subunit IV isoform I (COX4/1), which is an index of the amount of mitochondria in the cells that had been exposed to PQQ, PQQH 2 and IPQ. The results of the comparison showed that IPQ had almost the same biological activities as those of PQQ except for anti-oxidative activity. It was also shown that PQQ and IPQ improve the memory learning ability of aged mice and that BioPQQ® improves brain function in the language field in humans.