Regulation of cytosolic and mitochondrial ATP levels in mouse eggs and zygotes

Fertilization activates development by stimulating a plethora of ATP consuming processes that must be provided for by an up-regulation of energy production in the zygote. Sperm-triggered Ca(2+) oscillations are known to be responsible for the stimulation of both ATP consumption and ATP supply but the mechanism of up regulation of energy production at fertilization is still unclear. By measuring [Ca(2+)] and [ATP] in the mitochondria of fertilized mouse eggs we demonstrate that sperm entry triggers Ca(2+) oscillations in the cytosol that are transduced into mitochondrial Ca(2+) oscillations pacing mitochondrial ATP production. This results, during fertilization, in an increase in both [ATP](mito) and [ATP](cyto). We also observe the stimulation of ATP consumption accompanying fertilization by monitoring [Ca(2+)](cyto) and [ATP](cyto) during fertilization of starved eggs. Our observations reveal that lactate, in contrast to pyruvate, does not fuel mitochondrial ATP production in the zygote. Therefore lactate-derived pyruvate is somehow diverted from mitochondrial oxidation and may be channeled to other metabolic routes. Together with our earlier findings, this study confirms the essential role for exogenous pyruvate in the up-regulation of ATP production at the onset of development, and suggests that lactate, which does not fuel energetic metabolism may instead regulate the intracellular redox potential. (C) 2008 Elsevier Inc. All rights reserved.