PMID- 21367862
OWN - NLM
STAT- MEDLINE
DCOM- 20110701
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 18
DP  - 2011 May 6
TI  - Mouse knock-out of IOP1 protein reveals its essential role in mammalian cytosolic 
      iron-sulfur protein biogenesis.
PG  - 15797-805
LID - 10.1074/jbc.M110.201731 [doi]
AB  - Iron-sulfur proteins play an essential role in a variety of biologic processes 
      and exist in multiple cellular compartments. The biogenesis of these proteins has 
      been the subject of extensive investigation, and particular focus has been placed 
      on the pathways that assemble iron-sulfur clusters in the different cellular 
      compartments. Iron-only hydrogenase-like protein 1 (IOP1; also known as nuclear 
      prelamin A recognition factor like protein, or NARFL) is a human protein that is 
      homologous to Nar1, a protein in Saccharomyces cerevisiae that, in turn, is an 
      essential component of the cytosolic iron-sulfur protein assembly pathway in 
      yeast. Previous siRNA-induced knockdown studies using mammalian cells point to a 
      similar role for IOP1 in mammals. In the present studies, we pursued this further 
      by knocking out Iop1 in Mus musculus. We find that Iop1 knock-out results in 
      embryonic lethality before embryonic day 10.5. Acute, inducible global knock-out 
      of Iop1 in adult mice results in lethality and significantly diminished activity 
      of cytosolic aconitase, an iron-sulfur protein, in liver extracts. Inducible 
      knock-out of Iop1 in mouse embryonic fibroblasts results in diminished activity 
      of cytosolic but not mitochondrial aconitase and loss of cell viability. 
      Therefore, just as with knock-out of Nar1 in yeast, we find that knock-out of 
      Iop1/Narfl in mice results in lethality and defective cytosolic iron-sulfur 
      cluster assembly. The findings demonstrate an essential role for IOP1 in this 
      pathway.
FAU - Song, Daisheng
AU  - Song D
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania 
      School of Medicine, Philadelphia, Pennsylvania 19104, USA.
FAU - Lee, Frank S
AU  - Lee FS
LA  - eng
GR  - R01 GM071459/GM/NIGMS NIH HHS/United States
GR  - R01-GM71459/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110302
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CIAO3 protein, human)
RN  - 0 (Iron-Sulfur Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 70FD1KFU70 (Sulfur)
RN  - E1UOL152H7 (Iron)
RN  - EC 1.12.7.2 (Hydrogenase)
RN  - EC 1.12.7.2 (Nar1 protein, S cerevisiae)
RN  - EC 4.2.1.3 (Aconitate Hydratase)
SB  - IM
MH  - Aconitate Hydratase/genetics/metabolism
MH  - Animals
MH  - Cell Line
MH  - Embryo Loss/enzymology/genetics
MH  - Embryo, Mammalian/enzymology
MH  - Fibroblasts/enzymology
MH  - Humans
MH  - Hydrogenase/genetics/*metabolism
MH  - Iron/metabolism
MH  - Iron-Sulfur Proteins/*biosynthesis/genetics/metabolism
MH  - Liver/enzymology
MH  - Mice
MH  - Mice, Knockout
MH  - Saccharomyces cerevisiae/enzymology/genetics
MH  - Saccharomyces cerevisiae Proteins/genetics/metabolism
MH  - Sulfur/metabolism
PMC - PMC3091189
EDAT- 2011/03/04 06:00
MHDA- 2011/07/02 06:00
PMCR- 2012/05/06
CRDT- 2011/03/04 06:00
PHST- 2011/03/04 06:00 [entrez]
PHST- 2011/03/04 06:00 [pubmed]
PHST- 2011/07/02 06:00 [medline]
PHST- 2012/05/06 00:00 [pmc-release]
AID - S0021-9258(20)51398-7 [pii]
AID - M110.201731 [pii]
AID - 10.1074/jbc.M110.201731 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 May 6;286(18):15797-805. doi: 10.1074/jbc.M110.201731. Epub 
      2011 Mar 2.