A close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria.

Diffley, John F.X.; Stillman, Bruce

doi:10.1073/pnas.88.17.7864

Cited by 288 publications

(140 citation statements)

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“…The first representative of this large and heterogeneous family of proteins, Abf2p, was identified by biochemical means (15,16), and its gene was cloned by Diffley and Stillman (17). Abf2p contains two HMG box domains mediating nonspecific binding of the protein to DNA, accompanied by its bending and compaction (18,19).…”

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The Strictly Aerobic Yeast Yarrowia lipolytica Tolerates Loss of a Mitochondrial DNA-Packaging Protein

et al. 2014

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bMitochondrial DNA (mtDNA) is highly compacted into DNA-protein structures termed mitochondrial nucleoids (mt-nucleoids). The key mt-nucleoid components responsible for mtDNA condensation are HMG box-containing proteins such as mammalian mitochondrial transcription factor A (TFAM) and Abf2p of the yeast Saccharomyces cerevisiae. To gain insight into the function and organization of mt-nucleoids in strictly aerobic organisms, we initiated studies of these DNA-protein structures in Yarrowia lipolytica. We identified a principal component of mt-nucleoids in this yeast and termed it YlMhb1p (Y. lipolytica mitochondrial HMG box-containing protein 1). YlMhb1p contains two putative HMG boxes contributing both to DNA binding and to its ability to compact mtDNA in vitro. Phenotypic analysis of a ⌬mhb1 strain lacking YlMhb1p resulted in three interesting findings. First, although the mutant exhibits clear differences in mt-nucleoids accompanied by a large decrease in the mtDNA copy number and the number of mtDNA-derived transcripts, its respiratory characteristics and growth under most of the conditions tested are indistinguishable from those of the wild-type strain. Second, our results indicate that a potential imbalance between subunits of the respiratory chain encoded separately by nuclear DNA and mtDNA is prevented at a (post)translational level. Third, we found that mtDNA in the ⌬mhb1 strain is more prone to mutations, indicating that mtHMG box-containing proteins protect the mitochondrial genome against mutagenic events. Individual eukaryotic cells contain a population of mitochondrial DNA (mtDNA) molecules, the number of which may reach several thousand copies. For example, aerobically grown diploid cells of the yeast Saccharomyces cerevisiae contain, on average, 100 molecules of 85-kbp mtDNA. With a distance of 0.34 nm between base pairs in DNA, the total length of mtDNA reaches almost 3 mm per cell, while the diameter of the cell does not exceed 3 to 4 m. Analogously to its nuclear counterpart, mtDNA must be packaged into condensed nucleoprotein structures termed mitochondrial nucleoids (mt-nucleoids) (1-6). The size of mt-nucleoids in S. cerevisiae ranges from 0.2 to 0.9 m, meaning that mtDNA in yeasts undergoes compaction of roughly 3 orders of magnitude. Although it is known that the size and shape (oval versus globular) of mt-nucleoids, the number of mt-nucleoids (ranging from 50 to 70) per diploid cell (2), and the number of copies (up to 9) of mtDNA per mt-nucleoid (3) in S. cerevisiae depend on physiological conditions, the molecular mechanisms mediating nucleoid maintenance, dynamics, and roles in mtDNA distribution/segregation during cell division are largely not understood. This is also true for mammalian mt-nucleoids, which, in contrast to their yeast counterparts, contain a relatively small number of mtDNA molecules and are thus more solitary in nature (7,8). Description of these intra-and interspecific differences in the organization of mt-nucleoids would greatly facilitate our understanding of the m...

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The Strictly Aerobic Yeast Yarrowia lipolytica Tolerates Loss of a Mitochondrial DNA-Packaging Protein

et al. 2014

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“…Abf2 is a DNA-binding protein required for the maintenance of mtDNA on glucose (25,26). ABF2 null mutants are deficient in respiration (25). Together, these facts suggest that Ilv5 is required for the stability of the mitochondrial genome and that Tpk1 regulates mitochondrial proteins key to this process.…”

Section: Tpk1 Regulates Genes Of the Branched Chain Amino Acid Pathwamentioning

confidence: 99%

“…Overexpression of ILV5, but not ILV2, another branched chain amino acid pathway gene, suppresses the mutant phenotype of abf2 strains (24). Abf2 is a DNA-binding protein required for the maintenance of mtDNA on glucose (25,26). ABF2 null mutants are deficient in respiration (25).…”

Section: Tpk1 Regulates Genes Of the Branched Chain Amino Acid Pathwamentioning

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The yeast A kinases differentially regulate iron uptake and respiratory function

Robertson

Causton

Young

et al. 2000

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

161

150

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Tpk2, but not Tpk1 or Tpk3, is required for pseudohyphal growth. Genome-wide transcriptional profiling has revealed unique signatures for each of the three A kinases leading to the identification of additional functional diversity among these proteins. Tpk2 negatively regulates genes involved in iron uptake and positively regulates genes involved in trehalose degradation and water homeostasis. Tpk1 is required for the derepression of branched chain amino acid biosynthesis genes that seem to have a second role in the maintenance of iron levels and DNA stability within mitochondria. The fact that TPK2 mutants grow better than wild types on nonfermentable carbon sources and on media deficient in iron supports the unique role of Tpk2 in respiratory growth and carbon source use.I n yeast, cAMP acting through the A kinases (PKA) provides a key regulatory signal for growth on diverse carbon sources. Growth on fermentable carbon sources (e.g., glucose, fructose, and sucrose) requires a higher basal level of cAMP than does growth on nonfermentable carbon sources (e.g., ethanol, glycerol, and acetate). Therefore, the level of cAMP must decrease in order for cells to switch from growth on fermentable carbon sources to growth on nonfermentable carbon sources (the diauxic shift; ref. 1). Addition of glucose to yeast cells growing on a nonfermentable carbon source or starved for glucose results in a transient peak in intracellular cAMP levels. This transition to fermentation requires both the transient increase of cAMP and the cAMP-dependent PKA (2). Activated PKA shifts the metabolic flux away from gluconeogenesis and toward glycolysis by regulating key enzymes in these processes including fructose-1,6-bisphosphatase and phosphofructokinase-2 (3). Phosphorylation by PKA inactivates the transcription factor Adr1, a positive regulatory factor for the transcription of the respiratory enzyme Adh2 (4). In addition, PKA promotes the breakdown of glycogen and trehalose by inhibiting enzymes involved in synthesis (trehalose synthase and glycogen synthase) and activating enzymes involved in breakdown (trehalase and glycogen phosphorylase) of these storage carbohydrates.The transcriptional changes occurring in the transition from fermentative growth to respiratory growth have been monitored by genome expression arrays (5). As glucose is depleted, transcription of genes involved in respiration, the tricarboxylic acid cycle, the glyoxylate cycle, gluconeogenesis, and storage carbohydrate synthesis is induced, whereas transcription of genes involved in glycolysis and protein synthesis is repressed (5). Consistent with the shift to respiratory growth, cytoplasmic ribosomal protein genes are repressed, and mitochondrial ribosomal genes are induced. In view of the role of cAMP and the PKAs in the use of carbon sources, these results raise the question of whether the PKAs function in respiratory growth and whether they are redundant for this function.To elucidate more broadly the functional differences between the PKA catalytic subunits, we ...

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“…h-TFAM was also shown to be required for specific initiation at mitochondrial promoters in vitro (14 -17). The yeast homologue of TFAM is Abf2p, an abundant protein whose primary role is to stabilize and compact mtDNA (21)(22)(23); however, Abf2p is not required for transcription of yeast mtDNA (24). Both human mtTFB1 and mt-TFB2 have been shown to activate transcription from mitochondrial promoters in vitro, although their specific roles in mitochondrial transcription remain unclear (14,15,25).…”

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Drosophila Mitochondrial Transcription Factor B2 Regulates Mitochondrial DNA Copy Number and Transcription in Schneider Cells

Matsushima

Garesse

Kaguni

2004

Journal of Biological Chemistry

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We report the cloning and molecular analysis of Drosophila mitochondrial transcription factor B2 (d-mt-TFB2), a protein that plays a role in mitochondrial transcription and mitochondrial DNA (mtDNA) replication in Drosophila. An RNA interference (RNAi) construct was designed that reduces expression of d-mtTFB2 to 5% of its normal level in Schneider cells. RNAi knock-down of d-mtTFB2 reduces the abundance of specific mitochondrial RNA transcripts 2-to 8-fold and decreases the copy number of mtDNA ϳ3-fold. In a corollary manner, we find that overexpression of d-mtTFB2 increases both the abundance of mitochondrial RNA transcripts and the copy number of mtDNA. In a comparative experiment, we find that overexpression of Drosophila mitochondrial transcription factor A (d-TFAM) increases mtDNA copy number with no significant effect on mitochondrial transcripts. This argues for a direct role for mtTFB2 in mitochondrial transcription and suggests that, if TFAM serves a role in transcription, its endogenous level limits mtDNA copy number but not transcription. Furthermore, we suggest that mtTFB2 increases mtDNA copy number by increasing the frequency of initiation of DNA replication, whereas TFAM serves to stabilize and package mtDNA in mitochondrial nucleoids. Our work represents the first study to document the function of mtTFB2 in vivo, establishing a dual role in regulation of both transcription and replication, and provides a benchmark for comparative biochemical studies in various animal systems.The mitochondria of eukaryotic cells utilize a number of organelle-specific factors in DNA and RNA metabolism. In Saccharomyces cerevisiae, mitochondrial transcription is mediated by the yeast mtRNA 1 polymerase, Rpo41p (1-3), and a specificity factor Mtf1p (4 -6), also known as mitochondrial transcription factor B (sc-mtTFB) (7). Deficiency in sc-mtTFB lowers the abundance of mitochondrial transcripts and reduces mtDNA copy number (5, 7). sc-mtTFB facilitates specific binding of mitochondrial RNA polymerase at numerous promoter sites in the yeast mitochondrial genome (4,8,9). Although sc-mtTFB is functionally similar to bacterial sigma factor (9 -11), the two proteins do not share amino acid sequence (7,12) or structural homology (13). Rather, the structure of sc-mtTFB is homologous to bacterial rRNA methyltransferases (13).Mammalian mitochondrial transcription utilizes mitochondrial RNA polymerase, and three distinct transcription factors: transcription factor A (TFAM; formerly referred to as mtTFA) and two proteins homologous to sc-mtTFB, transcription factors mtTFB1 and mtTFB2 (3, 14 -17). TFAM contains two high mobility group boxes and was shown in organello to bind nonspecifically at regularly phased intervals to the control region of human mtDNA (18); it has recently been shown to package mtDNA in nucleoids (19,20). h-TFAM was also shown to be required for specific initiation at mitochondrial promoters in vitro (14 -17). The yeast homologue of TFAM is Abf2p, an abundant protein whose primary role is to stabilize and c...

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A close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria.

Cited by 288 publications

References 34 publications

The Strictly Aerobic Yeast Yarrowia lipolytica Tolerates Loss of a Mitochondrial DNA-Packaging Protein

The Strictly Aerobic Yeast Yarrowia lipolytica Tolerates Loss of a Mitochondrial DNA-Packaging Protein

The yeast A kinases differentially regulate iron uptake and respiratory function

Drosophila Mitochondrial Transcription Factor B2 Regulates Mitochondrial DNA Copy Number and Transcription in Schneider Cells

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