[Frontiers in Bioscience E4, 690-699, January 1, 2012]

The emerging roles of prohibitins in folliculogenesis

Indrajit Chowdhury1,2, Minerva Garcia-Barrio3, Djana Harp1,2, Kelwyn Thomas2,4, Roland Matthews1, Winston E. Thompson1,2

1Department of Obstetrics and Gynecology, , Morehouse School of Medicine, Atlanta, Georgia 30310, USA, 2Reproductive Science Research Program, , Morehouse School of Medicine, Atlanta, Georgia 30310, USA, 3Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia 30310, USA, 4Department of Neurobiology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Prohibitins
4. Gonadotropins synergize with androgens in the induction of prohibitins
5. Subcellular localization of prohibitins
6. Role of prohibitins in the inhibition of cell proliferation
7. Role of prohibitins in differentiation
8. Prohibitins phosphorlyation in cell differentiation
9. Role of prohibitins in cell apoptosis and atresia
10. Future directions
11. Conclusions
12. Acknowledgments
13. References

1. ABSTRACT

Prohibitins are members of a highly conserved eukaryotic protein family containing the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain (also known as the prohibitin (PHB) domain) found in divergent species from prokaryotes to eukaryotes. Prohibitins are found in unicellular eukaryotes, fungi, plants, animals and humans. Prohibitins are ubiquitously expressed and present in multiple cellular compartments including the mitochondria, nucleus, and the plasma membrane, and shuttles between the mitochondria, cytosol and nucleus. Multiple functions have been attributed to the mitochondrial and nuclear prohibitins, including cellular differentiation, anti-proliferation, and morphogenesis. In the present review, we focus on the recent developments in prohibitins research related to folliculogenesis. Based on current research findings, the data suggest that these molecules play important roles in modulating specific responses of granulose cells to follicle stimulating hormone (FSH) by acting at multiple levels of the FSH signal transduction pathway. Understanding the molecular mechanisms by which the intracellular signaling pathways utilize prohibitins in governing folliculogenesis is likely to result in development of strategies to overcome fertility disorders and suppress ovarian cancer growth.