title: Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: lvillene@unmc.edu.
authors.forename: Lance M
authors.initials: LM
authors.lastname: Villeneuve
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: kelly.stauch@unmc.edu.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Stauch
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: hfox@unmc.edu.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D016716:PC12 Cells; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat
keywords: Bioenergetics/electron transfer complex; Development; Mitochondria; Neurodegeneration; Oxidative stress