Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands

Lance M. Villeneuve, Kelly L. Stauch, Howard S Fox

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Many biological processes converge on the mitochondria. In such systems, where many pathways converge, manipulation of the components can produce varied and far-reaching effects. Due to the centrality of the mitochondria in many cellular pathways, we decided to investigate the brain mitochondrial proteome during early development. Using a SWATH mass spectrometry-based technique, we were able to identify vast proteomic alterations between whole brain mitochondria from rats at embryonic day 18 compared to postnatal day 7. These findings include statistically significant alterations in proteins involved in glycolysis and mitochondrial trafficking/dynamics. Additionally, bioinformatic analysis enabled the identification of HIF1A and XBP1 as upstream transcriptional regulators of many of the differentially expressed proteins. These data suggest that the cell is rearranging the mitochondria to accommodate special energy demands and that cytosolic proteins exert mitochondrial effects through dynamic interactions with the mitochondria. Biological significance: Although mitochondria play critical roles in many cellular pathways, our understanding of how these organelles change over time is limited. The changes occurring in the mitochondria at early time points are especially important as many mitochondrial disorders produce neurological dysfunction early in life. Herein, we utilize a SWATH mass spectrometry approach to quantify proteomic alterations of rat brain mitochondria between embryonic and postnatal stages. We found this method to be highly reproducible, enabling the identification of alterations in many biochemical pathways and mitochondrial properties. This insight into the distinct changes in these biological pathways to maintain homeostasis under divergent conditions will help elucidate the pathological changes occurring in disease states.

Original languageEnglish (US)
Pages (from-to)228-239
Number of pages12
JournalJournal of Proteomics
Volume109
DOIs
StatePublished - Sep 23 2014

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Mitochondria
Proteomics
Rats
Brain
Mass spectrometry
Mass Spectrometry
Mitochondrial Dynamics
Biological Phenomena
Mitochondrial Diseases
Mitochondrial Proteins
Glycolysis
Proteome
Bioinformatics
Computational Biology
Organelles
Proteins
Homeostasis

Keywords

  • Bioenergetics/electron transfer complex
  • Development
  • Mitochondria
  • Neurodegeneration
  • Oxidative stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands. / Villeneuve, Lance M.; Stauch, Kelly L.; Fox, Howard S.

In: Journal of Proteomics, Vol. 109, 23.09.2014, p. 228-239.

Research output: Contribution to journalArticle

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