Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1α expression

Winyoo Chowanadisai, Kathryn A. Bauerly, Eskouhie Tchaparian, Alice Wong, Gino A Cortopassi, Robert B. Rucker

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Bioactive compounds reported to stimulate mitochondrial biogenesis are linked to many health benefits such increased longevity, improved energy utilization, and protection from reactive oxygen species. Previously studies have shown that mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. Therefore, we hypothesized that PQQ can induce mitochondrial biogenesis in mouse hepatocytes. Exposure of mouse Hepa1-6 cells to 10-30 μM PQQ for 24-48 h resulted in increased citrate synthase and cytochrome c oxidase activity, Mitotracker staining, mitochondrial DNA content, and cellular oxygen respiration. The induction of this process occurred through the activation of cAMP response element-binding protein (CREB) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a pathway known to regulate mitochondrial biogenesis. PQQ exposure stimulated phosphorylation of CREB at serine 133, activated the promoter of PGC-1α, and increased PGC-1α mRNA and protein expression. PQQ did not stimulate mitochondrial biogenesis after small interfering RNA-mediated reduction in either PGC-1α or CREB expression. Consistent with activation of the PGC-1α pathway, PQQ increased nuclear respiratory factor activation (NRF-1 and NRF-2) and Tfam, TFB1M, and TFB2M mRNA expression. Moreover, PQQ protected cells from mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction.

Original languageEnglish (US)
Pages (from-to)142-152
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number1
DOIs
StatePublished - Jan 1 2010

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PQQ Cofactor
Cyclic AMP Response Element-Binding Protein
Phosphorylation
Organelle Biogenesis
Chemical activation
Nuclear Respiratory Factors
Cell Respiration
Antimycin A
Rotenone
Citrate (si)-Synthase
Sodium Azide
Messenger RNA
Peroxisome Proliferator-Activated Receptors
Insurance Benefits
Electron Transport Complex IV
Nutrition
Mitochondrial DNA
Serine
Small Interfering RNA
Rats

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1α expression. / Chowanadisai, Winyoo; Bauerly, Kathryn A.; Tchaparian, Eskouhie; Wong, Alice; Cortopassi, Gino A; Rucker, Robert B.

In: Journal of Biological Chemistry, Vol. 285, No. 1, 01.01.2010, p. 142-152.

Research output: Contribution to journalArticle

Chowanadisai, Winyoo ; Bauerly, Kathryn A. ; Tchaparian, Eskouhie ; Wong, Alice ; Cortopassi, Gino A ; Rucker, Robert B. / Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1α expression. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 1. pp. 142-152.
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