Identification of the mitochondrial heme metabolism complex

Amy E. Medlock, Mesafint T. Shiferaw, Jason R. Marcero, Ajay A. Vashisht, James A. Wohlschlegel, John D. Phillips, Harry A. Dailey

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Heme is an essential cofactor for most organisms and all metazoans. While the individual enzymes involved in synthesis and utilization of heme are fairly well known, less is known about the intracellular trafficking of porphyrins and heme, or regulation of heme biosynthesis via protein complexes. To better understand this process we have undertaken a study of macromolecular assemblies associated with heme synthesis. Herein we have utilized mass spectrometry with coimmunoprecipitation of tagged enzymes of the heme biosynthetic pathway in a developing erythroid cell culture model to identify putative protein partners. The validity of these data obtained in the tagged protein system is confirmed by normal porphyrin/heme production by the engineered cells. Data obtained are consistent with the presence of a mitochondrial heme metabolism complex which minimally consists of ferrochelatase, protoporphyrinogen oxidase and aminolevulinic acid synthase-2. Additional proteins involved in iron and intermediary metabolism as well as mitochondrial transporters were identified as potential partners in this complex. The data are consistent with the known location of protein components and support a model of transient protein-protein interactions within a dynamic protein complex.

Original languageEnglish (US)
Article numbere0135896
JournalPloS one
Volume10
Issue number8
DOIs
StatePublished - Aug 19 2015

Fingerprint

heme
Heme
Metabolism
metabolism
Proteins
porphyrins
Porphyrins
proteins
Protoporphyrinogen Oxidase
Ferrochelatase
protoporphyrinogen oxidase
Aminolevulinic Acid
aminolevulinic acid
Erythroid Cells
synthesis
Biosynthesis
Biosynthetic Pathways
Protein Biosynthesis
protein-protein interactions
Enzymes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Medlock, A. E., Shiferaw, M. T., Marcero, J. R., Vashisht, A. A., Wohlschlegel, J. A., Phillips, J. D., & Dailey, H. A. (2015). Identification of the mitochondrial heme metabolism complex. PloS one, 10(8), [e0135896]. https://doi.org/10.1371/journal.pone.0135896

Identification of the mitochondrial heme metabolism complex. / Medlock, Amy E.; Shiferaw, Mesafint T.; Marcero, Jason R.; Vashisht, Ajay A.; Wohlschlegel, James A.; Phillips, John D.; Dailey, Harry A.

In: PloS one, Vol. 10, No. 8, e0135896, 19.08.2015.

Research output: Contribution to journalArticle

Medlock, AE, Shiferaw, MT, Marcero, JR, Vashisht, AA, Wohlschlegel, JA, Phillips, JD & Dailey, HA 2015, 'Identification of the mitochondrial heme metabolism complex', PloS one, vol. 10, no. 8, e0135896. https://doi.org/10.1371/journal.pone.0135896
Medlock AE, Shiferaw MT, Marcero JR, Vashisht AA, Wohlschlegel JA, Phillips JD et al. Identification of the mitochondrial heme metabolism complex. PloS one. 2015 Aug 19;10(8). e0135896. https://doi.org/10.1371/journal.pone.0135896
Medlock, Amy E. ; Shiferaw, Mesafint T. ; Marcero, Jason R. ; Vashisht, Ajay A. ; Wohlschlegel, James A. ; Phillips, John D. ; Dailey, Harry A. / Identification of the mitochondrial heme metabolism complex. In: PloS one. 2015 ; Vol. 10, No. 8.
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