TY - JOUR
T1 - Structure, function, and assembly of heme centers in mitochondrial respiratory complexes
AU - Kim, Hyung J.
AU - Khalimonchuk, Oleh
AU - Smith, Pamela M.
AU - Winge, Dennis R.
N1 - Funding Information:
We acknowledge the grant support from the National Institutes of Health , GM083292 and ES03817 to D.R.W. H.J.K. and P.M.S. were supported by training grant T32 DK007115 . O.K. was supported by American Heart Association grant 10POST4300044 .
PY - 2012/9
Y1 - 2012/9
N2 - 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.
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.
KW - Cytochrome c oxidase
KW - Heme
KW - Mitochondria
KW - Respiration
KW - Succinate dehydrogenase
KW - Ubiquinol cytochrome c oxidoreductase
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U2 - 10.1016/j.bbamcr.2012.04.008
DO - 10.1016/j.bbamcr.2012.04.008
M3 - Review article
C2 - 22554985
AN - SCOPUS:84864309529
SN - 0167-4889
VL - 1823
SP - 1604
EP - 1616
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 9
ER -