A Protein Complex Containing Mdm10p, Mdm12p, and Mmm1p Links Mitochondrial Membranes and DNA to the Cytoskeleton-based Segregation Machinery

Boldogh, István; Nowakowski, Dan W.; Yang, Hyeong‐Cheol; Chung, Haesung; Karmon, Sharon L.; Royes, Patrina; Pon, Liza A.

doi:10.1091/mbc.e03-04-0225

Cited by 243 publications

(223 citation statements)

References 39 publications

(44 reference statements)

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“…The binding of actin to mitochondrial nucleoids has been reported by us and by the other investigators (Boldogh et al, 2003;Dai et al, 2005;Wang and Bogenhagen, 2006). We suggest here that mtDNA-bound actin may mediate the movement and segregation of mtDNA directly or indirectly, and it may play an important role in mtDNA inheritance.…”

Section: Discussionsupporting

confidence: 75%

“…We suggest here that mtDNA-bound actin may mediate the movement and segregation of mtDNA directly or indirectly, and it may play an important role in mtDNA inheritance. Boldogh et al (2003) concluded that mtDNA is linked to cytosolic actin through the mitochondrial protein complex known as the mitochore, and that this interaction between mtDNA and actin is critical for mtDNA inheritance.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the Structure and DNA Complexity of Mung Bean Mitochondrial Nucleoids

Hsiao

Cheng

et al. 2011

Molecules and Cells

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Electron microscopic images of mitochondrial nucleoids isolated from mung bean seedlings revealed a relatively homogeneous population of particles, each consisting of a chromatin-like structure associated with a membrane component. Association of F-actin with mitochondrial nucleoids was also observed. The mitochondrial nucleoid structure identified in situ showed heterogeneous genomic organization. After pulsed-field gel electrophoresis (PFGE), a large proportion of the mitochondrial nucleoid DNA remained in the well, whereas the rest migrated as a 50-200 kb smear zone. This PFGE migration pattern was not affected by high salt, topoisomerase I or latrunculin B treatments; however, the mobility of a fraction of the fastmoving DNA decreased conspicuously following an in-gel ethidium-enhanced UV-irradiation treatment, suggesting that molecules with intricately compact structures were present in the 50-200 kb region. Approximately 70% of the mitochondrial nucleoid DNA molecules examined via electron microscopy were open circles, supercoils, complex forms, and linear molecules with interspersed sigmashaped structures and/or loops. Increased sensitivity of mtDNA to DNase I was found after mitochondrial nucleoids were pretreated with high salt. This result indicates that some loosely bound or peripheral DNA binding proteins protected the mtDNA from DNase I degradation.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Characterization of the Structure and DNA Complexity of Mung Bean Mitochondrial Nucleoids

Hsiao

Cheng

et al. 2011

Molecules and Cells

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“…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).…”

mentioning

confidence: 99%

Dynamic Localization of Trypanosoma brucei Mitochondrial DNA Polymerase ID

2012

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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...

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“…The authors observed that mutations in MDM31 and MDM32 are synthetically lethal with mutations in MMM1, MMM2, MDM10, and MDM12. Mmm1p, Mmm2p, Mdm10p, and Mdm12p were suggested to form the outer membrane protein scaffold and the mitochore, a mitochondrial protein complex implicated in sustaining proper shape of mitochondria, the organelle attachment to the actin cytoskeleton, and an efficient segregation of mitochondrial DNA (Burgess et al 1994;Sogo and Yaffe 1994;Berger et al 1997;Boldogh et al 1998Boldogh et al , 2003Hobbs et al 2001;Youngman et al 2004). On the basis of these genetic interactions and observed displacement of mitochondrial nucleoids, it was suggested that Mdm31p and Mdm32p are required to link mtDNA to the mitochore (Dimmer et al 2005).…”

Section: Discussionmentioning

confidence: 99%

A Screen for Nigericin-Resistant Yeast Mutants Revealed Genes Controlling Mitochondrial Volume and Mitochondrial Cation Homeostasis

et al. 2005

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Little is known about the regulation of ion transport across the inner mitochondrial membrane in Saccharomyces cerevisiae. To approach this problem, we devised a screening procedure for facilitating the identification of proteins involved in mitochondrial ion homeostasis. Taking advantage of the growth inhibition of yeast cells by electroneutral K 1 /H 1 ionophore nigericin, we screened for genetic mutations that would render cells tolerant to this drug when grown on a nonfermentable carbon source and identified several candidate genes including MDM31, MDM32, NDI1, YMR088C (VBA1), CSR2, RSA1, YLR024C, and YNL136W (EAF7). Direct examination of intact cells by electron microscopy indicated that mutants lacking MDM31 and/or MDM32 genes contain dramatically enlarged, spherical mitochondria and that these morphological abnormalities can be alleviated by nigericin. Mitochondria isolated from the Dmdm31 and Dmdm32 mutants exhibited limited swelling in an isotonic solution of potassium acetate even in the presence of an exogenous K 1 /H 1 antiport. In addition, growth of the mutants was inhibited on ethanol-containing media in the presence of high concentrations of salts (KCl, NaCl, or MgSO 4 ) and their mitochondria exhibited two-(Dmdm31 and Dmdm32) to threefold (Dmdm31Dmdm32) elevation in magnesium content. Taken together, these data indicate that Mdm31p and Mdm32p control mitochondrial morphology through regulation of mitochondrial cation homeostasis and the maintenance of proper matrix osmolarity.

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A Protein Complex Containing Mdm10p, Mdm12p, and Mmm1p Links Mitochondrial Membranes and DNA to the Cytoskeleton-based Segregation Machinery

Cited by 243 publications

References 39 publications

Characterization of the Structure and DNA Complexity of Mung Bean Mitochondrial Nucleoids

Characterization of the Structure and DNA Complexity of Mung Bean Mitochondrial Nucleoids

Dynamic Localization of Trypanosoma brucei Mitochondrial DNA Polymerase ID

A Screen for Nigericin-Resistant Yeast Mutants Revealed Genes Controlling Mitochondrial Volume and Mitochondrial Cation Homeostasis

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