PNPase knockout results in mtDNA loss and an altered metabolic gene expression program

PloS One
Eriko ShimadaMichael A Teitell

Abstract

Polynucleotide phosphorylase (PNPase) is an essential mitochondria-localized exoribonuclease implicated in multiple biological processes and human disorders. To reveal role(s) for PNPase in mitochondria, we established PNPase knockout (PKO) systems by first shifting culture conditions to enable cell growth with defective respiration. Interestingly, PKO established in mouse embryonic fibroblasts (MEFs) resulted in the loss of mitochondrial DNA (mtDNA). The transcriptional profile of PKO cells was similar to rho0 mtDNA deleted cells, with perturbations in cholesterol (FDR = 6.35 x 10-13), lipid (FDR = 3.21 x 10-11), and secondary alcohol (FDR = 1.04x10-12) metabolic pathway gene expression compared to wild type parental (TM6) MEFs. Transcriptome analysis indicates processes related to axonogenesis (FDR = 4.49 x 10-3), axon development (FDR = 4.74 x 10-3), and axonal guidance (FDR = 4.74 x 10-3) were overrepresented in PKO cells, consistent with previous studies detailing causative PNPase mutations in delayed myelination, hearing loss, encephalomyopathy, and chorioretinal defects in humans. Overrepresentation analysis revealed alterations in metabolic pathways in both PKO and rho0 cells. Therefore, we assessed the correlation of g...Continue Reading

References

Jul 2, 1984·European Journal of Biochemistry·M GrégoireD Gravel
Jul 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·J W YipC Capriotti
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·B K Mohanty, S R Kushner
Aug 7, 2002·Journal of Molecular Biology·Anne JarrigeClaude Portier
Nov 11, 1955·Science·M GRUNBERG-MANAGOS OCHOA
Mar 17, 2004·Molecular Phylogenetics and Evolution·Magdalena LeszczynieckaPaul B Fisher
Oct 27, 2004·Trends in Biochemical Sciences·Kris A Demali
Sep 8, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·V MateiB Fritzsch
Sep 13, 2006·Molecular and Cellular Biology·Hsiao-Wen ChenSamuel W French
Nov 7, 2006·Biochimie·Federica BrianiGianni Dehò
Jun 8, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suhua DengRohini Kuner
Aug 6, 2008·The Journal of Biological Chemistry·Lily KhidrWen-Hwa Lee
May 13, 2009·Nucleic Acids Research·Paula P CardenasJuan C Alonso
Jun 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Inna A BelyantsevaJames M Ervasti
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Swadesh K DasPaul B Fisher
Aug 10, 2010·Cell·Geng WangMichael A Teitell
Feb 24, 2011·Wiley Interdisciplinary Reviews. RNA·Bijoy K Mohanty, Sidney R Kushner
Apr 13, 2011·PloS One·Brette D BlakelyClare L Parish
Oct 7, 2011·Wiley Interdisciplinary Reviews. RNA·Inês Jesus SilvaCecília Maria Arraiano
Feb 11, 2012·Microbiology·Devashish RathNarendra Jawali
Mar 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Geng WangCarla M Koehler
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He

❮ Previous
Next ❯

Datasets Mentioned

BETA
MMU04110
GSE111668
MMU00100

Methods Mentioned

BETA
PCR
fluorescence microscopy
RNA-Seq
flow cytometry
transgenic
Illumina sequencing
lateral shearing interferometry

Software Mentioned

ORA
DESeq2
PROSize
R Bioconductor
pheatmap
package
FlowJo
GraphPad Prism
Bioconductor
clusterProfiler

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.