Evidence map›Paper›PMID 19036724›Full record

ArticleThe Journal of biological chemistry2009

Short hairpin RNA-mediated silencing of PRC (PGC-1-related coactivator) results in a severe respiratory chain deficiency associated with the proliferation of aberrant mitochondria.

Kristel Vercauteren, Natalie Gleyzer, Richard C Scarpulla

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Hepatic microRNA Expression by PGC-1α and PGC-1β in the Mouse.International journal of molecular sciences · 2019
    Article
  11. Mechanisms of mammalian mitochondrial transcription.Protein science : a publication of the Protein Society · 2019
    Review
  12. Review
  13. Review
  14. Article
  15. NO control of mitochondrial function in normal and transformed cells.Biochimica et biophysica acta. Bioenergetics · 2017
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Role of mitochondria in nonalcoholic fatty liver disease.International journal of molecular sciences · 2014
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Kristel VercauterenDepartment of Cell and Molecular Biology, Northwestern Medical School, Chicago, Illinois 60611, USA.
Natalie Gleyzer
Richard C Scarpulla
Northwestern University · US

Funding

TRANSCRIPTIONAL CONTROL BY NUCLEAR RESPIRATORY FACTORSR01GM032525 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SCARPULLA, RICHARD · 1985 to 2012
$4.6M
Nuclear Control of Respiratory Chain ExpressionR56GM032525 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SCARPULLA, RICHARD · 2007 to 2007
$478k
NIGMS NIH HHS GM32525-26
6 · The paper itself

Abstract

PRC, a member of the PGC-1 coactivator family, is responsive to serum growth factors and up-regulated in proliferating cells. Here, we investigated its in vivo role by stably silencing PRC expression with two different short hairpin RNAs (shRNA1 and shRNA4) that were lentivirally introduced into U2OS cells. shRNA1 transductants exhibited nearly complete knockdown of PRC protein, whereas shRNA4 transductants expressed PRC protein at approximately 15% of the control level. Complete PRC silencing by shRNA1 resulted in a severe inhibition of respiratory growth; reduced expression of respiratory protein subunits from complexes I, II, III, and IV; markedly lower complex I and IV respiratory enzyme levels; and diminished mitochondrial ATP production. Surprisingly, shRNA1 transductants exhibited a striking proliferation of abnormal mitochondria that were devoid of organized cristae and displayed severe membrane abnormalities. Although shRNA4 transductants had normal respiratory subunit expression and a moderately diminished respiratory growth rate, both transductants showed markedly reduced growth on glucose accompanied by inhibition of G1/S cell cycle progression. Microarray analysis revealed striking overlaps in the genes affected by PRC silencing in the two transductants, and the functional identities of these overlapping genes were consistent with the observed mitochondrial and cell growth phenotypes. The consistency between phenotype and PRC expression levels in the two independent transductant lines argues that the defects result from PRC silencing and not from off target effects. These results support a role for PRC in the integration of pathways directing mitochondrial respiratory function and cell growth.

Indexed as

Nucleic Acid ConformationRNA InterferenceCell LineCell ProliferationHumansLentivirusMicroscopy, Electron, TransmissionMitochondriaMitochondrial DiseasesOligonucleotide Array Sequence AnalysisTranscription Factorsperoxisome-proliferator-activated receptor-gamma coactivator-1Transcription Factors

Identifiers

PMID19036724
PMCPMC2629116
OpenAlexW1969018223

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.