Functional consequences of mitochondrial proteome heterogeneity

D. Thor Johnson, Robert A. Harris, Paul V. Blair, Robert S. Balaban

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Potential functional consequences of the differences in protein distribution between the mitochondria of the rat liver, heart, brain, and kidney, as determined in the companion paper in this issue (Johnson DT, French S, Blair PV, You JS, Bemis KG, Wang M, Harris RA, and Balaban RS. The tissue heterogeneity of the mammalian mitochondrial proteome. Am J Physiol Cell Physiol 292: C689-C697, 2006), were analyzed using a canonical metabolic pathway approach as well as a functional domain homology analysis. These data were inserted into the Kyoto Encyclopedia of Genes and Genomes pathway framework to give global and metabolic pathway-specific information on the impact of the differential protein distribution on mitochondrial function. Custom pathway analysis was also performed using pathways limited to the mitochondrion. With the use of this approach, several well-known functional differences between these mitochondrial populations were confirmed. These included GABA metabolism in the brain, urea synthesis in the liver, and the domination of oxidative phosphorylation in the heart. By comparing relative protein amounts of mitochondria across tissues, a greater understanding of functional emphasis is possible as well as the nuclear "programming" required to enhance a given function within the mitochondria. For proteins determined to be mitochondrial and lacking a defined role functional domain BLAST analyses were performed. Several proteins associated with DNA structural modification and a novel CoA transferase were identified. A protein was also identified capable of catalyzing the first three steps of de novo pyrimidine synthesis. This analysis demonstrates that the distribution of nuclear encoded proteins significantly modifies the overall functional emphasis of the mitochondria to meet tissue-specific needs. These studies demonstrate the existence of mitochondrial biochemical functions that at present are poorly defined.

Original languageEnglish (US)
Pages (from-to)C698-C707
JournalAmerican Journal of Physiology - Cell Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 1 2007

Fingerprint

Proteome
Mitochondria
Proteins
Tissue
Metabolic Networks and Pathways
Liver
Brain
Genes
Coenzyme A-Transferases
Encyclopedias
Liver Mitochondrion
Oxidative Phosphorylation
Nuclear Proteins
Metabolism
gamma-Aminobutyric Acid
Urea
Rats
Genome
Kidney
DNA

Keywords

  • Brain
  • Electrophoresis
  • Heart
  • Histone
  • Kidney
  • Liquid chromatography
  • Liver
  • Mass spectrometry
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Functional consequences of mitochondrial proteome heterogeneity. / Johnson, D. Thor; Harris, Robert A.; Blair, Paul V.; Balaban, Robert S.

In: American Journal of Physiology - Cell Physiology, Vol. 292, No. 2, 01.02.2007, p. C698-C707.

Research output: Contribution to journalArticle

Johnson, D. Thor ; Harris, Robert A. ; Blair, Paul V. ; Balaban, Robert S. / Functional consequences of mitochondrial proteome heterogeneity. In: American Journal of Physiology - Cell Physiology. 2007 ; Vol. 292, No. 2. pp. C698-C707.
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