Surprisingly, we find that even in the absence of starvation, autophagy may play an important role in the normal turnover of mitochondria and that inhibition of autophagy by IGF-I can lead to mitochondrial dysfunction and decreased cell viability. Because mitochondrial mutations and dysfunction may increase with age may be significant to age-related pathologic conditions. A unique feature of mammalian oocytes is that transcription ceases upon oocyte maturation and does not resume until embryonic transcription becomes activated in the early embryo. During this period of transcriptional quiescence, the oocyte must rely on maternal factors, structures, and organelles that have accumulated in the oocyte during growth to mediate this critical period, often called the oocyte-to-embryo transition. In non-mammalian species, mutation analysis has identified a large number of factors, called maternal effect genes, which are synthesized and accumulate in the oocyte and then persist in the early embryo where they are required for embryonic development. Additionally, PADI6 has also been putatively identified as a component of the SCMC complex. While FILIA is thought to play a role in chromosome stability during embryogenesis, the role of MATER remains to be elucidated. PADI6 was originally cloned from the mouse oocyte proteome due to its abundance in metaphase II-arrested oocytes and its oocyte-restricted expression pattern. Interestingly, PADI6 is localized to, and required for, the formation of an abundant, oocyte- and early embryo-restricted structure, the cytoplasmic lattices. The lattices are composed of 5–7 parallel fibers with each fiber containing a repeating unit of,20 nm. The bundled fibers are first observed at early stages of oocyte growth and persist in the early embryo until the SP600125 blastocyst stage. CPLs were found to be resistant to Triton-X-100, thus, extraction with this detergent provides a valuable tool for studying CPL associated proteins. While CPLs have been observed by electron microscopy since the 1960s, their function remains poorly understood. Based on electron microscopy and biochemical analysis, a number of older reports predicted that the lattices may function as yolk granules or as a ribosomal storage site, with the latter hypothesis being supported by recent data from our lab. Microarray analysis along with previous studies suggest that both transcripts appear in the oocyte at the primordial/primary follicle stage and then abruptly disappear around meiotic maturation. MATER and PADI6 protein expression roughly parallels that of their transcripts in oocytes; however, protein levels persist at high levels throughout preimplantation development until the blastocyst stage. In this manuscript, we define a new role for MATER by showing that this maternal effect gene product appears to be required for CPL formation. At the subcellular level, these proteins appear to co-localize at the oocyte subcortex and this localization becomes asymmetrically restricted to apical cytocortex of two-cell embryos.
The reduced clearance of dysfunctional mitochondria in settings where IGF-I is elevated
Leave a reply