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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice¹

Tracy Stites^*, David Storms^*, Kathryn Bauerly^*, James Mah^**, Calliandra Harris^*, Andrea Fascetti, Quinton Rogers, Eskouhie Tchaparian^*, Michael Satre^* and Robert B. Rucker^*,2

^* Department of Nutrition (College of Agriculture and Environmental Sciences) and Department of Molecular Biosciences (School of Veterinary Medicine), University of California, Davis, CA 95616; and ^** Department of Dentistry, University of Southern California, Los Angeles, CA 90089

² To whom correspondence should be addressed.rbrucker{at}ucdavis.edu.

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 µg 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 µg DPI/g BW. The PQQ-deficient mice exposed to 0.4 or 4.0 µg DPI/g lost weight and had lower plasma glucose levels than PQQ-supplemented mice (P < 0.05). In addition, fibroblasts took up ³H-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.

KEY WORDS: • pyrroloquinoline quinone • mitochondria • diphenylene iodonium • respiratory control • respiratory quotient

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