Structure, function, and assembly of heme centers in mitochondrial respiratory complexes

Hyung J. Kim, Oleh Khalimonchuk, Pamela M. Smith, Dennis R. Winge

Research output: Contribution to journalReview article

77 Citations (Scopus)

Abstract

The sequential flow of electrons in the respiratory chain, from a low reduction potential substrate to O 2, is mediated by protein-bound redox cofactors. In mitochondria, hemes-together with flavin, iron-sulfur, and copper cofactors-mediate this multi-electron transfer. Hemes, in three different forms, are used as a protein-bound prosthetic group in succinate dehydrogenase (complex II), in bc 1 complex (complex III) and in cytochrome c oxidase (complex IV). The exact function of heme b in complex II is still unclear, and lags behind in operational detail that is available for the hemes of complex III and IV. The two b hemes of complex III participate in the unique bifurcation of electron flow from the oxidation of ubiquinol, while heme c of the cytochrome c subunit, Cyt1, transfers these electrons to the peripheral cytochrome c. The unique heme a 3, with Cu B, form a catalytic site in complex IV that binds and reduces molecular oxygen. In addition to providing catalytic and electron transfer operations, hemes also serve a critical role in the assembly of these respiratory complexes, which is just beginning to be understood. In the absence of heme, the assembly of complex II is impaired, especially in mammalian cells. In complex III, a covalent attachment of the heme to apo-Cyt1 is a prerequisite for the complete assembly of bc 1, whereas in complex IV, heme a is required for the proper folding of the Cox 1 subunit and subsequent assembly. In this review, we provide further details of the aforementioned processes with respect to the hemes of the mitochondrial respiratory complexes. This article is part of a Special Issue entitled: Cell Biology of Metals.

Original languageEnglish (US)
Pages (from-to)1604-1616
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1823
Issue number9
DOIs
StatePublished - Sep 1 2012

Fingerprint

Heme
Electrons
Cytochromes c
Succinate Dehydrogenase
Electron Transport Complex IV
Electron Transport
Sulfur
Oxidation-Reduction
Cell Biology
Copper
Catalytic Domain
Mitochondria
Proteins
Iron
Metals
Oxygen

Keywords

  • Cytochrome c oxidase
  • Heme
  • Mitochondria
  • Respiration
  • Succinate dehydrogenase
  • Ubiquinol cytochrome c oxidoreductase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Structure, function, and assembly of heme centers in mitochondrial respiratory complexes. / Kim, Hyung J.; Khalimonchuk, Oleh; Smith, Pamela M.; Winge, Dennis R.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1823, No. 9, 01.09.2012, p. 1604-1616.

Research output: Contribution to journalReview article

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AB - The sequential flow of electrons in the respiratory chain, from a low reduction potential substrate to O 2, is mediated by protein-bound redox cofactors. In mitochondria, hemes-together with flavin, iron-sulfur, and copper cofactors-mediate this multi-electron transfer. Hemes, in three different forms, are used as a protein-bound prosthetic group in succinate dehydrogenase (complex II), in bc 1 complex (complex III) and in cytochrome c oxidase (complex IV). The exact function of heme b in complex II is still unclear, and lags behind in operational detail that is available for the hemes of complex III and IV. The two b hemes of complex III participate in the unique bifurcation of electron flow from the oxidation of ubiquinol, while heme c of the cytochrome c subunit, Cyt1, transfers these electrons to the peripheral cytochrome c. The unique heme a 3, with Cu B, form a catalytic site in complex IV that binds and reduces molecular oxygen. In addition to providing catalytic and electron transfer operations, hemes also serve a critical role in the assembly of these respiratory complexes, which is just beginning to be understood. In the absence of heme, the assembly of complex II is impaired, especially in mammalian cells. In complex III, a covalent attachment of the heme to apo-Cyt1 is a prerequisite for the complete assembly of bc 1, whereas in complex IV, heme a is required for the proper folding of the Cox 1 subunit and subsequent assembly. In this review, we provide further details of the aforementioned processes with respect to the hemes of the mitochondrial respiratory complexes. This article is part of a Special Issue entitled: Cell Biology of Metals.

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