Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α Signaling Pathway

Biochemistry. 2017 Dec 19;56(50):6615-6625. doi: 10.1021/acs.biochem.7b01185. Epub 2017 Dec 6.


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.

MeSH terms

  • Animals
  • Benzoquinones / chemistry
  • Benzoquinones / metabolism
  • Fibroblasts
  • Hep G2 Cells
  • Humans
  • Mice
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • NIH 3T3 Cells
  • Organelle Biogenesis
  • Oxidation-Reduction
  • PQQ Cofactor / chemistry
  • PQQ Cofactor / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Signal Transduction / drug effects
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism


  • Benzoquinones
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Trans-Activators
  • Transcription Factors
  • quinone
  • PQQ Cofactor
  • SIRT1 protein, human
  • Sirt1 protein, mouse
  • Sirtuin 1