A role for the mitochondrial-associated protein p32 in regulation of trophoblast proliferation
Open Access
- 29 May 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Molecular Human Reproduction
- Vol. 20 (8), 745-755
- https://doi.org/10.1093/molehr/gau039
Abstract
P32 is a conserved eukaryotic protein which is primarily expressed in the mitochondria and regulates cell proliferation, migration and metabolism in various tissues. In this study, we sought to examine the expression and function of p32 in the human placenta. p32 was highly expressed in the syncytiotrophoblast, the underlying cytotrophoblast (CTB), the vascular endothelium and by a proportion of cells in the villous stroma in first trimester and term placenta. p32 mRNA and protein expression was significantly higher in the first trimester of pregnancy than at term, and expression in the trophoblast was significantly reduced in placentas from women with fetal growth restriction (FGR). Small interfering RNA (siRNA)-mediated knockdown of p32 in term placental explants significantly reduced the number of Ki67-positive CTB, but did not alter CTB apoptosis or necrosis. p32 knockdown increased lactate production, reduced glucose extraction from culture medium and was associated with reduced MitoTracker dye accumulation in trophoblast mitochondria. p32 knockdown was also associated with a significant reduction in expression of the mitochondrial respiratory complexes I and IV. These data suggest that p32 expression is important for CTB proliferation, via a mechanism involving regulation of normal mitochondrial function. As p32 expression is reduced in FGR placentas, this may contribute to some of the observed placental pathology, such as reduced CTB proliferation and mitochondrial dysfunction.Keywords
This publication has 38 references indexed in Scilit:
- p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survivalBiochemical Journal, 2013
- Comparative Proteomics Analysis Suggests that Placental Mitochondria are Involved in the Development of Pre-EclampsiaPLOS ONE, 2013
- Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survivalCell Death & Disease, 2013
- p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding abilityNucleic Acids Research, 2012
- Cell-surface Receptor for Complement Component C1q (gC1qR) Is a Key Regulator for Lamellipodia Formation and Cancer MetastasisJournal of Biological Chemistry, 2011
- IGF2 Actions on Trophoblast in Human Placenta Are Regulated by the Insulin-Like Growth Factor 2 Receptor, Which Can Function as Both a Signaling and Clearance Receptor1Biology of Reproduction, 2011
- Mitochondrial p32 Protein Is a Critical Regulator of Tumor Metabolism via Maintenance of Oxidative PhosphorylationMolecular and Cellular Biology, 2010
- Methods for siRNA-mediated Reduction of mRNA and Protein Expression in Human Placental Explants, Isolated Primary Cells and Cell LinesPlacenta, 2009
- Mitochondrial/Cell-Surface Protein p32/gC1qR as a Molecular Target in Tumor Cells and Tumor StromaCancer Research, 2008
- The contribution of gC1qR/p33 in infection and inflammationImmunobiology, 2007