TY - JOUR
T1 - Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice
AU - Stites, Tracy
AU - Storms, David
AU - Bauerly, Kathryn
AU - Mah, James
AU - Harris, Calliandra
AU - Fascetti, Andrea J
AU - Rogers, Quinton
AU - Tchaparian, Eskouhie
AU - Satre, Michael
AU - Rucker, Robert B.
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
KW - Diphenylene iodonium
KW - Mitochondria
KW - Pyrroloquinoline quinone
KW - Respiratory control
KW - Respiratory quotient
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M3 - Article
C2 - 16424117
AN - SCOPUS:32444431621
VL - 136
SP - 390
EP - 396
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 2
ER -