Prohibitin (PHB) roles in granulosa cell physiology

Abstract

Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on the recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/prohibitin/flotillin/HflK/C (SPFH) domain [also known as the PHB domain] found in divergent species from prokaryotes to eukaryotes. PHB is ubiquitously expressed either in circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane (IMM), and form complexes with the ATPases Associated with diverse cellular Activities (m-AAA) proteases. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulate transcriptional activity directly or through interactions with chromatin remodeling proteins. Multiple functions have been attributed to the mitochondrial and nuclear prohibitin complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintaining the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood.

Effect of 3-nitropropionic acid inducing oxidative stress and apoptosis of granulosa cells in geese

“…Several studies have suggested that numerous ROS are produced by the ovaries in female animals during folliculogenesis and ovulation [ 5 , 6 ]. Granulosa cells, which surround oocytes in ovaries, play a pivotal role in follicular development, ovulation, atresia and steroidogenesis [ 7 , 8 ]. It is well known that oxidative stress induces granulosa cell apoptosis, which plays a vital role in initiating follicular atresia [ 9–11 ].…”

Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation

“…In addition, PHB phosphorylation sites also occur within the Raf1 binding domain of PHB (residues 243–272). The MEK1-ERK1/2-signaling pathway is known to be involved in GC survival ( Moore et al 2001 , Dewi et al 2002 , Amsterdam et al 2003 , Su et al 2006 , Woods & Johnson 2007 , Duarte et al 2014 , Chowdhury et al 2016 ). Thus, based on our unpublished phosphosite bioinformatic studies using complete PHB amino acid sequences, we developed our own custom-made pPHB antibodies.…”

“…Prohibitin (PHB) is a member of the highly conserved ubiquitous protein family and plays a pleiotropic role in cell cycle control, differentiation, and senescence, in addition to having antiproliferative and anti-apoptotic roles ( Chowdhury et al 2016 ). A growing body of experimental evidence implicates PHB in the maintenance of integrity of mitochondrial structure, functions, inheritance, and cellular homeostasis ( Thompson et al 1999 , 2001 , 2003 , Sutovsky et al 2000 , Kawashima et al 2006, 2008, Artal-Sanz & Tavernarakis 2009 , Chowdhury et al 2016 ). Recently, PHB has been identified as a substrate for Ras-Raf and Akt, and is essential for activation of the Ras-Raf-MEK1-ERK1/2 signaling pathway ( Rajalingam et al 2005 , Han et al 2008 ).…”

Proteomic Analysis of Thermal Regulation of Small Yellow Follicles in Broiler-Type Taiwan Country Chickens

“…The decreased abundances of cytoskeleton proteins such as DES, SPARC, VIM, and ASMA in SYFs might lead to cellular differentiation and ovulatory process failure. In addition, the downregulation of GUCY1B2 may alter FSH-stimulated E2 production and decrease the regulation of PHB, and thus, disturb the activity of tissue repair and folliculogenesis (Tafoya et al, 2004;Chowdhury et al, 2016). In addition, the abundances of PDIA4 and GRP78, related to ER stress and cell apoptosis (Tufo et al, 2014), were increased in SYFs after acute heat stress.…”