Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27(Kip1) expression.
Reactive oxygen species (ROS) steady-state levels are required for entry into the S phase of the cell cycle in normal cells, as well as in tumour cells. However, the contribution of mitochondrial ROS to normal cell proliferation has not been well investigated thus far. A previous report showed that Romo1 was responsible for the high ROS levels in tumour cells. Here, we show that endogenous ROS generated by Romo1 are indispensable for cell cycle transition from G1 to S phase in normal WI-38 human lung fibroblasts. The ROS level in these cells was down-regulated by Romo1 knockdown, resulting in cell cycle arrest in the G1 phase. This arrest was associated with an increase in the level of p27(Kip1). These results demonstrate that mitochondrial ROS generated by Romo1 expression is required for normal cell proliferation and it is suggested that Romo1 plays an important role in redox signalling during normal cell proliferation.
Chung
Jin Sil
JS
Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul, 136-705, Republic of Korea.
Lee
Seung Baek
SB
Park
Seon Ho
SH
Kang
Sung Tae
ST
Na
Ah Ram
AR
Chang
Tong-Shin
TS
Kim
Hyung Jung
HJ
Yoo
Young Do
YD
D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C513338:ROMO1 protein, human; D017382:Reactive Oxygen Species; D050760:Cyclin-Dependent Kinase Inhibitor p27