Molecular genetics of succinate:quinone oxidoreductase in eukaryotes.
Succinate:quinone oxidoreductase is a membrane-associated complex in mitochondria, often referred to as complex II, based on the fractionation scheme developed by Y. Hatefi and colleagues. It consists of four peptides, two of which are integral membrane proteins (15 and 12-13 kDa, respectively) and two others that are peripheral membrane proteins, i.e., a flavoprotein (Fp, 70 kDa) and an iron-protein (Ip, 27 kDa). The mature, functional complex contains a cytochrome in association with the membrane proteins, a flavin linked covalently to the largest peptide, and three iron-sulfur clusters in the 27-kDa subunit. The present review touches only briefly on the biochemical and biophysical properties of this complex. Instead, the focus is on the molecular-genetic studies that have become possible since the first genes from eukaryotes were cloned in 1989. The evolutionary conservation of the amino acid sequence of both the Fp and the Ip peptides has facilitated the cloning of these genes from a large variety of eukaryotic organisms by PCR-based methods. The review addresses questions related to the regulation of the expression of these genes, with an emphasis on mammals and yeast, for which most of the information is available. Four different genes have to be co-ordinately regulated. Transcriptional as well as posttranscriptional regulatory mechanisms have been observed in diverse organisms. Intriguing observations have been made in studies of this enzyme during the life cycle of organisms existing alternately under aerobic and anaerobic conditions. Naturally occurring or induced mutations in these genes have shed light on several questions related to the assembly of this complex, and on the relationship between structure and function. Four different peptides are imported into the mitochondria. They have to be modified, folded, and assembled. The stage is set for the exploration of highly specific changes introduced by site-directed mutagenesis. Until recently the genes were believed to be exclusively nuclear in all eukaryotes, but exceptions have since been found. This finding has relevance in the discussion of the evolution of mitochondria from prokaryotes. A highly conserved set of genes is found in prokaryotes, and some informative comparisons on gene organization and expression in prokaryotes and eukaryotes have been included.
Scheffler
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Department of Biology, University of California, San Diego 92093, USA.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004579:Electron Transport; D042963:Electron Transport Complex II; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008967:Molecular Biology; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013385:Succinate Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D009097:Multienzyme Complexes; D004247:DNA; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase