PMID- 29185343
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20171227
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Linking)
VI  - 56
IP  - 50
DP  - 2017 Dec 19
TI  - Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial 
      Biogenesis by Activating the SIRT1/PGC-1alpha Signaling Pathway.
PG  - 6615-6625
LID - 10.1021/acs.biochem.7b01185 [doi]
AB  - 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-gamma-coactivator 1alpha 
      (PGC-1alpha) 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-1alpha-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-1alpha 
      signaling pathway by enhancing cellular NAD(+) formation.
FAU - Saihara, Kazuhiro
AU  - Saihara K
AD  - Department of Biological Chemistry, Division of Applied Life Science, Graduate 
      School of Life and Environmental Sciences, Osaka Prefecture University , Sakai 
      599-8531, Japan.
FAU - Kamikubo, Ryosuke
AU  - Kamikubo R
AD  - Department of Biological Chemistry, Division of Applied Life Science, Graduate 
      School of Life and Environmental Sciences, Osaka Prefecture University , Sakai 
      599-8531, Japan.
AD  - Department of Applied Biological Chemistry, Graduate School of Agricultural and 
      Life Sciences, University of Tokyo , Tokyo 113-8657, Japan.
FAU - Ikemoto, Kazuto
AU  - Ikemoto K
AUID- ORCID: 0000-0002-5708-1636
AD  - Niigata Research Laboratory, Mitsubishi Gas Chemical Company, Inc. , Niigata 
      950-3112, Japan.
FAU - Uchida, Koji
AU  - Uchida K
AD  - Department of Applied Biological Chemistry, Graduate School of Agricultural and 
      Life Sciences, University of Tokyo , Tokyo 113-8657, Japan.
FAU - Akagawa, Mitsugu
AU  - Akagawa M
AUID- ORCID: 0000-0002-8735-4738
AD  - Department of Biological Chemistry, Division of Applied Life Science, Graduate 
      School of Life and Environmental Sciences, Osaka Prefecture University , Sakai 
      599-8531, Japan.
LA  - eng
PT  - Journal Article
DEP - 20171206
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Benzoquinones)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 3T006GV98U (quinone)
RN  - 72909-34-3 (PQQ Cofactor)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Benzoquinones/chemistry/metabolism
MH  - Fibroblasts
MH  - Hep G2 Cells
MH  - Humans
MH  - Mice
MH  - Mitochondria/metabolism/physiology
MH  - NIH 3T3 Cells
MH  - Organelle Biogenesis
MH  - Oxidation-Reduction
MH  - PQQ Cofactor/chemistry/*metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 
      1-alpha/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/genetics/*metabolism
MH  - Trans-Activators/metabolism
MH  - Transcription Factors/metabolism
EDAT- 2017/12/01 06:00
MHDA- 2017/12/28 06:00
CRDT- 2017/11/30 06:00
PHST- 2017/12/01 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
PHST- 2017/11/30 06:00 [entrez]
AID - 10.1021/acs.biochem.7b01185 [doi]
PST - ppublish
SO  - Biochemistry. 2017 Dec 19;56(50):6615-6625. doi: 10.1021/acs.biochem.7b01185. 
      Epub 2017 Dec 6.