title: Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice.
abstract: When pyrroloquinoline quinone (PQQ) is added to an amino acid-based, but otherwise nutritionally complete basal diet, it improves growth-related variables in young mice. We examined PQQ and mitochondrial function based on observations that PQQ deficiency results in elevated plasma glucose concentrations in young mice, and PQQ addition stimulates mitochondrial complex 1 activity in vitro. PQQ-deficient weanling mice had a 20-30% reduction in the relative amount of mitochondria in liver; lower respiratory control ratios, and lower respiratory quotients than PQQ-supplemented mice (2 mg PQQ/kg diet). In mice from dams fed a conventional laboratory diet, but switched at weaning to the basal diet, plasma glucose, Ala, Gly, and Ser concentrations were elevated at 4 wk (PQQ- vs. PQQ+), but not at 8 wk. The relative mitochondrial content (ratio of mtDNA to nuclear DNA) also tended (P<0.18) to be lower (PQQ- vs. PQQ+) at 4 wk, but not at 8 wk. PQQ also counters the mitochondrial complex 1 inhibitor, diphenylene iodonium (DPI). Mice were gavaged with 0, 0.4, or 4 microg PQQ/g body weight (BW) daily for 14 d. At each PQQ level, DPI was injected (i.p.) at 0, 0.4, 0.8, or 1.6 microg DPI/g BW. The PQQ-deficient mice exposed to 0.4 or 4.0 microg DPI/g lost weight and had lower plasma glucose levels than PQQ-supplemented mice (P<0.05). In addition, fibroblasts took up (3)H-PQQ added to cell cultures, and cultured hepatocytes maintained mitochondrial PQQ concentrations similar to those observed in vivo. Collectively, these results indicate that dietary PQQ can influence mitochondrial amount and function, particularly in perinatal and weanling mice.
authors.affiliation: Department of Nutrition (College of Agriculture and Environmental Sciences), Los Angeles, CA 90089, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Stites
authors.forename: David
authors.initials: D
authors.lastname: Storms
authors.forename: Kathryn
authors.initials: K
authors.lastname: Bauerly
authors.forename: James
authors.initials: J
authors.lastname: Mah
authors.forename: Calliandra
authors.initials: C
authors.lastname: Harris
authors.forename: Andrea
authors.initials: A
authors.lastname: Fascetti
authors.forename: Quinton
authors.initials: Q
authors.lastname: Rogers
authors.forename: Eskouhie
authors.initials: E
authors.lastname: Tchaparian
authors.forename: Michael
authors.initials: M
authors.lastname: Satre
authors.forename: Robert B
authors.initials: RB
authors.lastname: Rucker
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics; D005347:Fibroblasts; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D045542:PQQ Cofactor / Q000494:pharmacology*; D051381:Rats
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D004272:DNA, Mitochondrial; D019344:Lactic Acid; D045542:PQQ Cofactor