Mitochondrial signaling and fertilization.

The magnitude of the potential difference (polarity) across the inner mitochondrial membrane (DeltaPsim) determines levels of several mitochondrial activities, including ATP generation, focal regulate calcium homeostasis and organelle volume homeostasis. We investigated whether a domain of mitochondria in the mouse oocyte, characterized by high DeltaPsim and a unique location in the subplasmalemmal cytoplasm, is involved in the earliest events of fertilization: sperm attachment, penetration and cortical granule exocytosis. Experimental manipulations of the magnitude of DeltaPsim and the distribution of mitochondria in zona-free MII oocytes, followed by insemination and culture, indicate that high-polarized mitochondria (HPM) are required for penetration and cortical granule exocytosis, but not for persistent attachment to the oolemma. The capacity of subplasmalemmal mitochondria to undergo transient reductions (dissipations) of DeltaPsim appears necessary for penetration and cortical granule exocytosis. We suggest that the HPM normally establish a continuous circumferential circuit of 'reactive' organelles capable of responding to and propagating, triggering or activating signals across the subplasmalemmal cytoplasm, such as those initiated by the fertilizing sperm at the site of penetration. The HPM in the oocyte and early embryo may have functions similar to those of their somatic cell counterparts and promote the focal regulation of developmental activities that are themselves spatially localized. The establishment of high DeltaPsim in the subplasmalemmal cytoplasm may be among the first steps in the preovulatory maturation of the oocyte and defects in this domain may result in fertilization failure or abnormality.