PMID- 19680543
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20220321
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 5
IP  - 8
DP  - 2009 Aug
TI  - A computational screen for regulators of oxidative phosphorylation implicates 
      SLIRP in mitochondrial RNA homeostasis.
PG  - e1000590
LID - 10.1371/journal.pgen.1000590 [doi]
LID - e1000590
AB  - The human oxidative phosphorylation (OxPhos) system consists of approximately 90 
      proteins encoded by nuclear and mitochondrial genomes and serves as the primary 
      cellular pathway for ATP biosynthesis. While the core protein machinery for 
      OxPhos is well characterized, many of its assembly, maturation, and regulatory 
      factors remain unknown. We exploited the tight transcriptional control of the 
      genes encoding the core OxPhos machinery to identify novel regulators. We 
      developed a computational procedure, which we call expression screening, which 
      integrates information from thousands of microarray data sets in a principled 
      manner to identify genes that are consistently co-expressed with a target pathway 
      across biological contexts. We applied expression screening to predict dozens of 
      novel regulators of OxPhos. For two candidate genes, CHCHD2 and SLIRP, we show 
      that silencing with RNAi results in destabilization of OxPhos complexes and a 
      marked loss of OxPhos enzymatic activity. Moreover, we show that SLIRP plays an 
      essential role in maintaining mitochondrial-localized mRNA transcripts that 
      encode OxPhos protein subunits. Our findings provide a catalogue of potential 
      novel OxPhos regulators that advance our understanding of the coordination 
      between nuclear and mitochondrial genomes for the regulation of cellular energy 
      metabolism.
FAU - Baughman, Joshua M
AU  - Baughman JM
AD  - Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 
      USA.
FAU - Nilsson, Roland
AU  - Nilsson R
FAU - Gohil, Vishal M
AU  - Gohil VM
FAU - Arlow, Daniel H
AU  - Arlow DH
FAU - Gauhar, Zareen
AU  - Gauhar Z
FAU - Mootha, Vamsi K
AU  - Mootha VK
LA  - eng
GR  - R01 GM077465/GM/NIGMS NIH HHS/United States
GR  - R01 GM077465-04/GM/NIGMS NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090814
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (RNA, Mitochondrial)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (SLIRP protein, human)
RN  - 0 (SLIRP protein, mouse)
RN  - 63231-63-0 (RNA)
SB  - IM
EIN - PLoS Genet. 2010;6(3). doi: 
      10.1371/annotation/36fe7624-0904-46d4-a013-4be6195245c4
MH  - Animals
MH  - Cell Line
MH  - Computational Biology/*methods
MH  - *Homeostasis
MH  - Humans
MH  - Mice
MH  - Mitochondria/chemistry/genetics/*metabolism
MH  - Oxidative Phosphorylation
MH  - RNA/chemistry/genetics/*metabolism
MH  - RNA, Mitochondrial
MH  - RNA-Binding Proteins/genetics/*metabolism
PMC - PMC2721412
COIS- The authors have declared that no competing interests exist.
EDAT- 2009/08/15 09:00
MHDA- 2009/10/29 06:00
PMCR- 2009/08/01
CRDT- 2009/08/15 09:00
PHST- 2009/03/03 00:00 [received]
PHST- 2009/07/09 00:00 [accepted]
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
PHST- 2009/08/01 00:00 [pmc-release]
AID - 09-PLGE-RA-0345R2 [pii]
AID - 10.1371/journal.pgen.1000590 [doi]
PST - ppublish
SO  - PLoS Genet. 2009 Aug;5(8):e1000590. doi: 10.1371/journal.pgen.1000590. Epub 2009 
      Aug 14.