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Prohibitin 2 Regulates the Proliferation and Lineage-Specific Differentiation of Mouse Embryonic Stem Cells in Mitochondria
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 4, p e81552 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- BackgroundThe pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown.Methodology/principal findingsIn this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria.Conclusions/significanceOur results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells.
- Subjects :
- Mitochondrial Diseases
Mitochondrial Myopathy
Science
Cellular differentiation
Induced Pluripotent Stem Cells
Mitochondrion
Biology
Cell Fate Determination
Cell Line
Mitochondrial Proteins
Mice
Animal Cells
Prohibitins
Genetics
Medicine and Health Sciences
Animals
Cell Lineage
Induced pluripotent stem cell
Embryonic Stem Cells
Cell Proliferation
Clinical Genetics
Regulation of gene expression
Mediator Complex
Multidisciplinary
Stem Cells
Biology and Life Sciences
Cell Differentiation
Human Genetics
Cell Biology
Embryonic stem cell
Mitochondria
Cell biology
Repressor Proteins
Gene Expression Regulation
mitochondrial fusion
Cell culture
Medicine
Cellular Types
Stem cell
Research Article
Developmental Biology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....956a4e5ae4803c80b724b75e38e5b9f0