RRC ID 62234
Author Kowno M, Watanabe-Susaki K, Ishimine H, Komazaki S, Enomoto K, Seki Y, Wang YY, Ishigaki Y, Ninomiya N, Noguchi TA, Kokubu Y, Ohnishi K, Nakajima Y, Kato K, Intoh A, Takada H, Yamakawa N, Wang PC, Asashima M, Kurisaki A.
Title Prohibitin 2 regulates the proliferation and lineage-specific differentiation of mouse embryonic stem cells in mitochondria.
Journal PLoS One
Abstract BACKGROUND:The 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 FINDINGS:In 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/SIGNIFICANCE:Our results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells.
Volume 9(4)
Pages e81552
Published 2014-1-1
DOI 10.1371/journal.pone.0081552
PII PONE-D-12-06851
PMID 24709813
PMC PMC3977857
MeSH Animals Cell Differentiation / physiology* Cell Line Cell Lineage / physiology* Cell Proliferation / physiology* Embryonic Stem Cells / cytology Embryonic Stem Cells / metabolism* Gene Expression Regulation / physiology Mediator Complex / biosynthesis Mediator Complex / genetics Mice Mitochondria / genetics Mitochondria / metabolism Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Repressor Proteins / genetics Repressor Proteins / metabolism*
IF 2.74
Human and Animal Cells 201B7(HPS0063)