Prohibitin 2 regulates the proliferation and lineage-specific differentiation of mouse embryonic stem cells in mitochondria

Megumi Kowno, Kanako Watanabe-Susaki, Hisako Ishimine, Shinji Komazaki, Kei Enomoto, Yasuhiro Seki, Ying Ying Wang, Yohei Ishigaki, Naoto Ninomiya, Taka Aki K. Noguchi, Yuko Kokubu, Keigoh Ohnishi, Yoshiro Nakajima, Kaoru Kato, Atsushi Intoh, Hitomi Takada, Norio Yamakawa, Pi Chao Wang, Makoto Asashima, Akira Kurisaki

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Article numbere81552
JournalPloS one
Volume9
Issue number4
DOIs
Publication statusPublished - 07-04-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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