Mitochondrial Transcription Is Regulated via an ATP “Sensing” Mechanism that Couples RNA Abundance to Respiration

Amiott, Elizabeth A.; Jaehning, Judith A.

doi:10.1016/j.molcel.2006.03.031

Cited by 98 publications

(84 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transcription from the human HSP1 and LSP is affected by ATP concentration (12,16), an effect that has also been observed at mitochondrial promoters in Saccharomyces cerevisiae (26). We found that increasing ATP concentration up to 100 μM stimulated both HSP1 and HSP2, which is in agreement with studies previously performed using recombinant proteins at HSP1 (16).…”

Section: Discussionsupporting

confidence: 91%

Transcriptional requirements of the distal heavy-strand promoter of mtDNA

Zollo

Tiranti

Sondheimer

2012

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

View full text Add to dashboard Cite

The heavy strand of mtDNA contains two promoters with nonoverlapping functions. The role of the minor heavy-strand promoter (HSP2) is controversial, because the promoter has been difficult to activate in an in vitro system. We have isolated HSP2 by excluding its interaction with the more powerful HSP1 promoter, and we find that it is transcribed efficiently by recombinant mtRNA polymerase and mitochondrial transcription factor B2. The mitochondrial transcription factor A is not required for initiation, but it has the ability to alternatively activate and repress the HSP2 transcriptional unit depending on the ratio between mitochondrial transcription factor A and other transcription factors. The positioning of transcriptional initiation agrees with our current understanding of HSP2 activity in vivo. Serial deletion of HSP2 shows that only proximal sequences are required. Several mutations, including the disruption of a polycytosine track upstream of the HSP2 initiation site, influence transcriptional activity. Transcription from HSP2 is also observed when HeLa cell mitochondrial extract is used as the source of mitochondrial polymerase, and this transcription is maintained when HSP2 is provided in proper spacing and context to the HSP1 promoter. Studies of the linked heavy-strand promoters show that they are differentially regulated by ATP dosage. We conclude that HSP2 is transcribed and has features that allow it to regulate mitochondrial mRNA synthesis.mitochondrial biology | organelle T he mitochondrial genome (mtDNA) encodes 13 proteins that are constituents of the electron transport chain and ATP synthase. Transcription of mtDNA proceeds bidirectionally, radiating out from the noncoding D-loop. The light-strand promoter (LSP) is required for the synthesis of ND6 mRNA and eight of the mitochondrial tRNAs (1). Transcription from LSP also primes the origin of heavy-strand replication, which is the first step in the synthesis of mtDNA (2).The heavy strand encodes 12 mRNAs, both mitochondrial rRNAs and the remaining tRNAs. Intracellular levels of mature rRNAs are in great excess to the mRNAs (3). Although it was initially proposed that this imbalance was caused by the existence of a single initiation site, with most primary transcripts terminating before reaching the protein coding region, later studies used a combination of ribonucleotide incorporation assays and capping of precursor transcripts to suggest the existence of two distinct heavy-strand initiation sites in close proximity (4-6). The first heavy-strand promoter (HSP1), which lies fully within the Dloop, is responsible for the synthesis of a transcript composed of the 12S and 16S rRNAs and intervening tRNAs (Fig. 1A). The minor or distal heavy-strand promoter (HSP2) initiates within the sequence of the mitochondrial tRNA for phenylalanine. HSP2-initiated transcription produces the remaining mitochondrial mRNAs by processing nearly the full length of the mtDNA.Studies of HSP2 promoter function are complicated by its unusual position, both within a tRNA-...

show abstract

Section: Discussionsupporting

confidence: 91%

Transcriptional requirements of the distal heavy-strand promoter of mtDNA

Zollo

Tiranti

Sondheimer

2012

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

View full text Add to dashboard Cite

show abstract

“…Our data are also consistent with the idea that the CoTP:ATP ratio is an important determinant for cordycepin toxicity, providing a plausible explanation of how poly(A) polymerase mutants suppressed cordycepin toxicity. Interestingly, a recent report revealed an ATP-sensing mechanism to connect RNA abundance to respiration (Amiott and Jaehning 2006). Our results suggest a reverse flow of information and raise the interesting possibility that the ''efficiency'' of gene expression (in this case, of polyadenylation) is somehow sensed and functionally linked to the energy status of the cell.…”

Section: Discussionmentioning

confidence: 59%

Cordycepin interferes with 3′ end formation in yeast independently of its potential to terminate RNA chain elongation

Holbein¹,

Wengi²,

Decourty³

et al. 2009

RNA

View full text Add to dashboard Cite

Cordycepin (39 deoxyadenosine) is a biologically active compound that, when incorporated during RNA synthesis in vitro, provokes chain termination due to the absence of a 39 hydroxyl moiety. We were interested in the effects mediated by this drug in vivo and analyzed its impact on RNA metabolism of yeast. Our results support the view that cordycepin-triphosphate (CoTP) is the toxic component that is limiting cell growth through inhibition of RNA synthesis. Unexpectedly, cordycepin treatment modulated 39 end heterogeneity of ACT1 and ASC1 mRNAs and rapidly induced extended transcripts derived from CYH2 and NEL025c loci. Moreover, cordycepin ameliorated the growth defects of poly(A) polymerase mutants and the pap1-1 mutation neutralized the effects of the drug on gene expression. Our observations are consistent with an epistatic relationship between poly(A) polymerase function and cordycepin action and suggest that a major mode of cordycepin activity reduces 39 end formation efficiency independently of its potential to terminate RNA chain elongation. Finally, chemical-genetic profiling revealed genome-wide pathways linked to cordycepin activity and identified novel genes involved in poly(A) homeostasis.

show abstract

“…However, the mechanism by which the chromatin structure in the nucleus affects the expression of genes carried by mitochondrial DNA is less obvious. A major mechanism that regulates the activity of the mitochondrial RNA polymerase Rpo41p/ Mtf1p in vitro is the concentration of ATP (70,71). To test whether this mechanism regulates the transcription of COX1, COX2, and COX3, three genes carried by mitochondrial DNA, we measured the corresponding transcript levels in spt10⌬ cells.…”

Section: Resultsmentioning

confidence: 99%

Reduced Histone Expression or a Defect in Chromatin Assembly Induces Respiration

Galdieri

Zhang

Rogerson

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

Regulation of mitochondrial biogenesis and respiration is a complex process that involves several signaling pathways and transcription factors as well as communication between the nuclear and mitochondrial genomes. Here we show that decreased expression of histones or a defect in nucleosome assembly in the yeast Saccharomyces cerevisiae results in increased mitochondrial DNA (mtDNA) copy numbers, oxygen consumption, ATP synthesis, and expression of genes encoding enzymes of the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). The metabolic shift from fermentation to respiration induced by altered chromatin structure is associated with the induction of the retrograde (RTG) pathway and requires the activity of the Hap2/3/4/5p complex as well as the transport and metabolism of pyruvate in mitochondria. Together, our data indicate that altered chromatin structure relieves glucose repression of mitochondrial respiration by inducing transcription of the TCA cycle and OXPHOS genes carried by both nuclear and mitochondrial DNA.

show abstract

Mitochondrial Transcription Is Regulated via an ATP “Sensing” Mechanism that Couples RNA Abundance to Respiration

Cited by 98 publications

References 67 publications

Transcriptional requirements of the distal heavy-strand promoter of mtDNA

Transcriptional requirements of the distal heavy-strand promoter of mtDNA

Cordycepin interferes with 3′ end formation in yeast independently of its potential to terminate RNA chain elongation

Reduced Histone Expression or a Defect in Chromatin Assembly Induces Respiration

Contact Info

Product

Resources

About