Regulation of mitochondrial biogenesis: Yeast mutants deficient in synthesis of δ-aminolevulinic acid

Sanders, Hildagarde K.; Mied, Paul A.; Briquet, Michel; Hernández‐Rodríguez, José; Gottal, R F; Mattoon, James R.

doi:10.1016/0022-2836(73)90231-3

Cited by 40 publications

(13 citation statements)

References 27 publications

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“…The results obtained with these certain labile iso-1 and iso-2-cytochromes c are reminiscent of the results obtained with certain heml mutations, which apparently encode labile forms of mitochondrial 8-aminolevulinic acid synthetase that are deficient in p-and [oxi2] strains but not in p+ strains (35,36). The 8-aminolevulinic acid synthetase deficiencies were more pronounced when the yeast was grown in glucose medium (36).…”

Section: Resultssupporting

confidence: 52%

Diminished degradation of yeast cytochrome c by interactions with its physiological partners.

Pearce

Sherman

1995

Proc. Natl. Acad. Sci. U.S.A.

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The level and structure of yeast iso-icytochrome c and iso-2-cytochrome c, encoded by the nuclear genes CYCI and CYC7, respectively, are normally not altered in p-mutants, which completely lack the cytochromes aa3 subunits and cytochrome b that are encoded by mitochondrial DNA. In contrast, iso-cytochromes c containing the amino acid change Thr-78 -> Ile (T781) were observed at the normal or near-normal wild-type level in p+ strains but were completely absent in p-mutants. We have demonstrated with the "global" suppressor mutation Asn-52 -* Ile and by pulsechase labeling that the T781 iso-l-cytochrome c undergoes rapid cellular degradation in p-mutants. Furthermore, specific mutations revealed that the deficiency of T781 iso-i cytochrome c can be caused by the lack of cytochrome a-a3 or cytochrome cl, but not by the lack of cytochrome b. Thus, this and certain other, but not all, labile forms of cytochrome c are protected from degradation by the interaction with its physiological partners.Iso-l-cytochrome c (iso-1) and iso-2-cytochrome c (iso-2) are encoded by the CYCl and CYC7 nuclear genes, respectively (1, 2) and these isocytochromes c are found at 95% and 5%, respectively, of the total cytochrome c complement in derepressed cells of the yeast Saccharomyces cerevisiae (3). Early studies revealed that the levels and structures of both isocytochromes c generally are equivalent in p+ and related pstrains-i.e., mutants that completely or partially lack mitochondrial DNA and do not carry out mitochondrial protein synthesis. This finding is consistent with CYCl and CYC7 being nuclear genes and suggested that the synthesis of the isocytochromes c is not significantly influenced by other mitochondrial deficiencies. In contrast, p-strains are completely deficient in cytochromes b and a-a3, a result explained by the fact that mitochondrial DNA encodes cytochrome b and three of the subunits of cytochrome a-a3 (4).The identification and characterization of the iso-2 structural gene, CYC7, in the yeast S. cerevisiae were initially carried out with the CYC7-H1 and CYC7-H3 mutations that caused overproduction of iso-2 because of abnormal promoters (2, 5, 6). The initial screens carried out in these studies relied on complete or partial loss of iso-2 in CYC7-H1 p-and CYC7-H3 p-strains, presumably due to alterations in the translated CYC7 region. Although equivalent amounts of iso-2 were observed in p+ and p-strains having the normal iso-2 sequence, surprisingly about one-third of the cyc7-H1 mutants had a greater deficiency in p-compared with p+ strains (7). In fact, iso-2 was completely deficient in some cyc7-HJ p-mutants, while iso-2 remained at the normal level in the corresponding cyc7-HJ p+ strain.In this study, we have demonstrated that certain amino acid replacements caused iso-1 and iso-2 to become susceptible to degradation preferentially in p-mutants. Furthermore, this increased sensitivity to degradation can arise by the absence ofThe publication costs of this article were defrayed in part by page charge p...

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Section: Resultssupporting

confidence: 52%

Diminished degradation of yeast cytochrome c by interactions with its physiological partners.

Pearce

Sherman

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…In yeasts and some bacteria, the consequence of a restriction in heme synthesis is a generalized diminution in the levels of all cytochromes (9,17,27,31,32,51,63). In DP104, however, syntheses of soluble periplasmic holo-c-type cytochromes are reduced to very low levels (2 to 3% of the wild-type levels by spectroscopy), while levels of membrane-bound c-type cytochromes are reduced by only 40 to 50%, roughly in line with other classes of membrane cytochrome.…”

Section: Resultsmentioning

confidence: 99%

Differential reduction in soluble and membrane-bound c-type cytochrome contents in a Paracoccus denitrificans mutant partially deficient in 5-aminolevulinate synthase activity

Page

Ferguson

1994

J Bacteriol

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A mutant of Paracoccus denitrificans, DP104, unable to grow anaerobically with nitrate as the terminal electron acceptor or aerobically with methanol as the electron donor and staining negatively in the dimethylphenylene diamine oxidation (Nadi) test, was isolated by transposon Tn5::phoA mutagenesis. P. denitrificans DP104 grown aerobically with succinate or choline had very low levels (2 to 3% of the wild-type levels) of spectroscopically detectable soluble c-type cytochromes. In contrast, membrane cytochromes of the a, b, and c types were present at 50% of the levels found in the wild type. The apo form of cytochrome c550, at an approximately 1:1 molar ratio with the holo form, was found in the periplasm of DP104. The TnphoA element was shown to be inserted immediately upstream of the translational start of hemA, the gene coding for 5-aminolevulinate synthase, which was sequenced. Low-level expression of this gene, driven off an incidental promoter provided by TnphoA-cointegrated suicide vector DNA, is the basis of the phenotype which could be complemented by the addition of 5-aminolevulinate to growth media. Disruption of the hemA gene generated a P. denitrificans strain auxotrophic for 5-aminolevulinate, establishing that there is no hemA-independent pathway of heme synthesis in this organism. The differential deficiency in periplasmic c-type cytochromes relative to membrane cytochromes in DP104 is suggested to arise from unequal competition for the restricted supply of heme which results from the effects of the transposon insertion.

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“…The latter studies also demonstrated that the enzyme is subject to catabolite repression and exhibits an oscillatory mode of synthesis. Sanders et al (1973) (Haslam et al, , 1973Rogers et al, 1974;Marzuki et al, 1975;Walenga & Lands, 1975) or sterol content (Parks & Starr, 1963;Thompson & Parks, 1974). Currently there is much interest in the assembly of the cytochromes in the mitochondrial membrane, particularly in cytochrome oxidase, whose biosynthesis resembles that of the inner mitochondrial membrane as a whole (for review see Schatz & Mason, 1974).…”

Section: Control Ofsterol Biosynthesis In Yeastmentioning

confidence: 99%

The manipulation of cellular cytochrome and lipid composition in a haem mutant of Saccharomyces cerevisiae

Astin¹,

Haslam²

1977

Biochemical Journal

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1. The ole-3 mutant of Saccharomyces cerevisiae has an early lesion in the pathway of porphyrin biosynthesis. 2. This results in the loss ofall haem-containing enzymes, including the mitochondrial cytochromes, and prevents the synthesis of components whose formation requires haem-containing enzymes, including unsaturated fatty acids, ergosterol and methionine. 3. The pleiotropic effects of the primary lesion are reversed by growing mutant ole-3 aerobically in the presence of intermediates of the porphyrin-biosynthetic pathway, and the present work reports the degree ofmanipulation oflipid and respiratorycytochrome composition. 4. Supplements of 5-aminolaevulinate in the range 0.5-500mg/l result in a progressive increase in the cellular content of unsaturated fatty acids and respiratory cytochromes, cause the replacement of lanosterol and squalene by ergosterol, and an increase in total sterol content. 5. Haematoporphyrin and protoporphyrin IX have similar but less extensive effects on cellular composition, whereas haematin allows unsaturated fatty acid synthesis and some sterol synthesis, but has no effect on the formation of respiratory cytochromes. 6. These results suggest that growth of the organism in the presence of defined amounts of 6-aminolaevulinate will be useful in the investigation of the role of lipids and cytochromes in the function and assembly of mitochondrial membranes.

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Regulation of mitochondrial biogenesis: Yeast mutants deficient in synthesis of δ-aminolevulinic acid

Cited by 40 publications

References 27 publications

Diminished degradation of yeast cytochrome c by interactions with its physiological partners.

Diminished degradation of yeast cytochrome c by interactions with its physiological partners.

Differential reduction in soluble and membrane-bound c-type cytochrome contents in a Paracoccus denitrificans mutant partially deficient in 5-aminolevulinate synthase activity

The manipulation of cellular cytochrome and lipid composition in a haem mutant of Saccharomyces cerevisiae

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