Evidence map›Paper›PMID 18980691›Full record

ArticleBMC genomics2008

mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft.

Darren Magda, Philip Lecane, Julia Prescott, Patricia Thiemann, Xuan Ma, Patricia K Dranchak, Donna M Toleno, Krishna Ramaswamy, Kimberly D Siegmund, Joseph G Hacia

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
0.8field-weighted citation impact, top 22% 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

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. Mitochondrial DNA Deficiency and Supplementation inInternational journal of molecular sciences · 2023
    Article
  4. Article
  5. Review
  6. Mitoepigenetics and Its Emerging Roles in Cancer.Frontiers in cell and developmental biology · 2020
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Oncogene-Driven Metabolic Alterations in Cancer.Biomolecules & therapeutics · 2018
    Review
  14. Review
  15. Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection.Biochimica et biophysica acta. Bioenergetics · 2017
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

10 authors at 2 institutions in 1 country.

Darren MagdaDepartment of Biochemistry and Molecular Biology, University of Southern California, 2250 Alcazar Street, IGM 240, Los Angeles, CA 90089, USA. dmagda@pcyc.com
Philip Lecane
Julia Prescott
Patricia Thiemann
Xuan Ma
Patricia K Dranchak
Donna M Toleno
Krishna Ramaswamy
Kimberly D Siegmund
Joseph G Hacia
University of Southern California · USPharmacyclics (United States) · US

Funding

RNA Programmed Translation RecodingR01GM072447 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BUTCHER, SAMUEL E · 2005 to 2016
$2.6M
Comparative Genomics of Peroxisomal Lipid MetabolismR01GM072477 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HACIA, JOSEPH G · 2005 to 2009
$1.8M
EXTRAMURAL RESEARCH FACILITIES CONTRUCTION PROJECTC06CA062528 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KEDES, LAURENCE H · 1993 to 1994
–
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR010600 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KEDES, LAURENCE H · 1994 to 1994
–
RESEARCH FACILITIES IMPROVEMENT PROGRAM AND REMODELINGC06RR014514 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KEDES, LAURENCE H · 1999 to 1999
–
NCI NIH HHS C06 CA062528NCI NIH HHS CA62528-01NCRR NIH HHS C06 RR014514NCRR NIH HHS RR10600-01NCRR NIH HHS RR14514-01NIGMS NIH HHS GM 072447NIGMS NIH HHS R01 GM072447NIGMS NIH HHS R01 GM072477
6 · The paper itself

Abstract

backgroundInteractions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in eukaryotic cellular function. However, the effects mitochondrial DNA (mtDNA) levels have on the nuclear transcriptome have not been defined under physiological conditions. In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted rho0 counterparts grown in culture and as tumor xenografts in immune-deficient mice.

resultsCultured A549 rho0 cells were respiration-deficient and showed enhanced levels of transcripts relevant to metal homeostasis, initiation of the epithelial-mesenchymal transition, and glucuronidation pathways. Several well-established HIF-regulated transcripts showed increased or decreased abundance relative to the parental cell line. Furthermore, growth in culture versus xenograft has a significantly greater influence on expression profiles, including transcripts involved in mitochondrial structure and both aerobic and anaerobic energy metabolism. However, both in vitro and in vivo, mtDNA levels explained the majority of the variance observed in the expression of transcripts in glucuronidation, tRNA synthetase, and immune surveillance related pathways. mtDNA levels in A549 xenografts also affected the expression of genes, such as AMACR and PHYH, involved in peroxisomal lipid metabolic pathways.

conclusionWe have identified mtDNA-dependent gene expression profiles that are shared in cultured cells and in xenografts. These profiles indicate that mtDNA-depleted cells could provide informative model systems for the testing the efficacy of select classes of therapeutics, such as anti-angiogenesis agents. Furthermore, mtDNA-depleted cells grown culture and in xenografts provide a powerful means to investigate possible relationships between mitochondrial activity and gene expression profiles in normal and pathological cells.

Indexed as

DNA, MitochondrialAnimalsCell NucleusCellsCells, CulturedGene Expression ProfilingGenome, HumanGenome, MitochondrialGenomicsHumansMiceTransplantation, HeterologousDNA, Mitochondrial

Identifiers

PMID18980691
PMCPMC2612029
OpenAlexW2160180709

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.