Impaired Mitochondrial Stress Response due to CLPP Deletion Is Associated with Altered Mitochondrial Dynamics and Increased Apoptosis in Cumulus Cells

  • E Esencan
  • Z Jiang
  • T Wang
  • M Zhang
  • G Soylemez-Imamoglu
  • E SeliEmail author
Original Article


Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) and is required for maintaining protein homeostasis in the mitochondria. Global germline Clpp deletion causes female infertility and accelerated follicular depletion. In the current study, we aimed to characterize the role of CLPP in cumulus cell function, gene expression, and mitochondrial ultrastructure. We found that mitochondria in Clpp-deficient cumulus cells have a smaller aspect ratio (length/width) and have a larger coverage area (mitochondrial area/cytoplasmic area) under electron microscopy. These ultrastructural changes were accompanied with diminished expression of mitochondrial dynamics genes. RNA sequencing analysis revealed a significant change in genes related to cellular metabolism in Clpp-deficient cumulus cells compared to wild type. In addition, apoptosis and phagosome pathways were significantly affected. Immunofluorescence assessment confirmed increased apoptotic activity and decreased cell proliferation in cumulus oophorus complexes (COCs) of Clpp-deficient mice. Our findings demonstrate that deletion of CLPP results in significant structural and functional changes in cumulus cells and suggests that mtUPR is required for cumulus cell function.


CLPP Cumulus cell Mitochondria Mitochondrial unfolded protein response 


Funding Information

E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence (FEC).

Supplementary material

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Copyright information

© Society for Reproductive Investigation 2020

Authors and Affiliations

  • E Esencan
    • 1
  • Z Jiang
    • 1
    • 2
  • T Wang
    • 1
    • 3
  • M Zhang
    • 1
  • G Soylemez-Imamoglu
    • 1
  • E Seli
    • 1
    Email author
  1. 1.Department of Obstetrics, Gynecology and Reproductive SciencesYale School of MedicineNew HavenUSA
  2. 2.AgCenter, School of Animal SciencesLouisiana State UniversityBaton RougeUSA
  3. 3.Foundation for Embryonic CompetenceBasking RidgeUSA

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