Mitochondrial nucleoids undergo remodeling in response to metabolic cues

Kucej, Martin; Kucejová, Blanka; Subramanian, Ramiah; Chen, Xin Jie; Butow, Ronald A.

doi:10.1242/jcs.028605

Cited by 99 publications

(86 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous mechanistic studies using purified recombinant mitochondrial transcription components led to the conclusion that the core human transcription machinery is an obligate threecomponent system comprising POLRMT, have been shown to change their composition as a way to adjust mtDNA expression in response to metabolic signals. 24 That mammalian nucleoids are also not packaged by mtTFA alone is consistent with this concept and has been proposed by others to dictate their relative activity with regard to transcription and replication. 22,[25][26][27] Other predictions of the h-mtTFAregulated two-component model are that significant transcription should persist when mtTFA levels are low or absent and that altering the mtTFA:mtDNA ratio should affect transcriptional output.…”

Section: Human Mitochondrial Transcription Initiation: Lessons From Psupporting

confidence: 76%

The core human mitochondrial transcription initiation complex

2011

View full text Add to dashboard Cite

Section: Human Mitochondrial Transcription Initiation: Lessons From Psupporting

confidence: 76%

The core human mitochondrial transcription initiation complex

2011

View full text Add to dashboard Cite

“…In vivo, Abf2p is essential for stabilization of mtDNA in cells grown on a fermentable carbon source such as glucose (Diffley & Stillman, 1991). In addition, it has been shown that Abf2p influences the level of yeast mtDNA recombination intermediates (MacAlpine et al, 1998) and is involved in remodelling of mt-nucleoids in response to changes in mitochondrial metabolism (Kucej et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Novel subfamily of mitochondrial HMG box-containing proteins: functional analysis of Gcf1p from Candida albicans

et al. 2009

View full text Add to dashboard Cite

Mitochondria of eukaryotic organisms contain populations of DNA molecules that are packed into higher-order structures called mitochondrial nucleoids (mt-nucleoids). In Saccharomyces cerevisiae, the compaction of mitochondrial DNA (mtDNA) into mt-nucleoids is mediated primarily by the high-mobility group (HMG) box-containing protein Abf2, which is an important player in stabilization and metabolism of mtDNA. Although it is evident that analogous proteins must exist in other yeast species, an apparently fast divergence rate has precluded their identification, characterization and comparative analysis. Using in silico analysis of the complete genome sequence of the pathogenic yeast Candida albicans we predicted that the ORF 19.400/19.8030 assigned as GCF1 encodes a putative mitochondrial HMG box-containing protein. In contrast to Abf2p, which contains two HMG boxes, Gcf1p contains only one C-terminal HMG box. In addition, it contains one putative coiled-coil domain with a potential role in protein dimerization. Fluorescence microscopy analysis of a C-terminally tagged Gcf1p with green fluorescent protein (GFP) revealed its mitochondrial localization in both heterologous (S. cerevisiae) and native (C. albicans) hosts. Biochemical analyses of DNA-binding properties indicate that Gcf1p is, similarly to Abf2p, a non-specific DNA-binding protein. To analyse the role of Gcf1p in mtDNA metabolism, we constructed strains lacking one functional allele of the GCF1 gene and carrying one GCF1 allele under the control of the MET3 promoter. Under repressible conditions this strain exhibited a more than 3000-fold decrease in levels of GCF1 mRNA, which was correlated with a substantial decrease in the number of mtDNA copies as well as recombination intermediates. The dramatic effect of reduced levels of Gcf1p on mtDNA metabolism indicates that the protein is involved in essential molecular transactions that relate to the mitochondrial genome.

show abstract

“…These structures are dynamic macrocomplexes located in the mitochondrial matrix, and they act as units of mtDNA replication and inheritance with composition that can undergo remodeling in response to metabolic stresses (7,23,47). Using bromodeoxyuridine (BrdU) incorporation, nucleoids have been shown to be the sites of mtDNA replication in yeast and mammalian cells (35,39).…”

mentioning

confidence: 99%

Dynamic Localization of Trypanosoma brucei Mitochondrial DNA Polymerase ID

2012

View full text Add to dashboard Cite

Trypanosomes contain a unique form of mitochondrial DNA called kinetoplast DNA (kDNA) that is a catenated network composed of minicircles and maxicircles. Several proteins are essential for network replication, and most of these localize to the antipodal sites or the kinetoflagellar zone. Essential components for kDNA synthesis include three mitochondrial DNA polymerases TbPOLIB, TbPOLIC, and TbPOLID). In contrast to other kDNA replication proteins, TbPOLID was previously reported to localize throughout the mitochondrial matrix. This spatial distribution suggests that TbPOLID requires redistribution to engage in kDNA replication. Here, we characterize the subcellular distribution of TbPOLID with respect to the Trypanosoma brucei cell cycle using immunofluorescence microscopy. Our analyses demonstrate that in addition to the previously reported matrix localization, TbPOLID was detected as discrete foci near the kDNA. TbPOLID foci colocalized with replicating minicircles at antipodal sites in a specific subset of the cells during stages II and III of kDNA replication. Additionally, the TbPOLID foci were stable following the inhibition of protein synthesis, detergent extraction, and DNase treatment. Taken together, these data demonstrate that TbPOLID has a dynamic localization that allows it to be spatially and temporally available to perform its role in kDNA replication.M itochondrial DNA (mtDNA) is packaged into protein-DNA complexes called nucleoids. These structures are dynamic macrocomplexes located in the mitochondrial matrix, and they act as units of mtDNA replication and inheritance with composition that can undergo remodeling in response to metabolic stresses (7,23,47). Using bromodeoxyuridine (BrdU) incorporation, nucleoids have been shown to be the sites of mtDNA replication in yeast and mammalian cells (35,39). However, not all nucleoids replicate concurrently; only a subset undergo replication at any given time. With no strict control related to cell cycle progression, the segregation and inheritance of the nucleoid depends upon a membrane-associated apparatus that interacts with the fusion and fission machinery of the mitochondrial organelle network (2,19,31). Lastly, while the protein composition of nucleoids varies among cell types and in response to metabolic conditions, the core proteins of the nucleoid appear to remain constant and include transcription and replication factors, such as mitochondrial transcription factor A, single-stranded binding protein, Twinkle helicase, and the sole mitochondrial DNA polymerase, Pol ␥ (1, 21).One of the most unusual and structurally complex mtDNA genomes is found in trypanosomatid parasites such as Trypanosoma brucei, the causative agent of African sleeping sickness. This extranuclear genome, called kinetoplast DNA (kDNA), is a network composed of thousands of topologically interlocked minicircles and maxicircles that are condensed into a single diskshaped nucleoid structure. Approximately 25 identical maxicircle copies (23 kb) encode a subset of respiratory c...

show abstract

Mitochondrial nucleoids undergo remodeling in response to metabolic cues

Cited by 99 publications

References 37 publications

The core human mitochondrial transcription initiation complex

The core human mitochondrial transcription initiation complex

Novel subfamily of mitochondrial HMG box-containing proteins: functional analysis of Gcf1p from Candida albicans

Dynamic Localization of Trypanosoma brucei Mitochondrial DNA Polymerase ID

Contact Info

Product

Resources

About