Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre-implantation embryos.

ABSTRACT: Caseinolytic peptidase P mediates degradation of unfolded mitochondrial proteins and activates mitochondrial unfolded protein response (mtUPR) to maintain protein homeostasis. Clpp^-/- female mice generate a lower number of mature oocytes and two-cell embryos, and no blastocysts. Clpp^-/- oocytes have smaller mitochondria, with lower aspect ratio (length/width), and decreased expression of genes that promote fusion. A 4-fold increase in atretic follicles at 3 months, and reduced number of primordial follicles at 6-12 months are observed in Clpp^-/- ovaries. This is associated with upregulation of p-S6, p-S6K, p-4EBP1 and p-AKT473, p-mTOR2481 consistent with mTORC1 and mTORC2 activation, respectively, and Clpp^-/- oocyte competence is partially rescue

SUBMITTER: Wang T 

PROVIDER: S-EPMC6052477 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature