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  1. Article ; Online: Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae.

    Schrott, Simon / Osman, Christof

    Nucleic acids research

    2023  Volume 51, Issue 21, Page(s) 11813–11835

    Abstract: The mitochondrial genome, mtDNA, is present in multiple copies in cells and encodes essential subunits of oxidative phosphorylation complexes. mtDNA levels have to change in response to metabolic demands and copy number alterations are implicated in ... ...

    Abstract The mitochondrial genome, mtDNA, is present in multiple copies in cells and encodes essential subunits of oxidative phosphorylation complexes. mtDNA levels have to change in response to metabolic demands and copy number alterations are implicated in various diseases. The mitochondrial HMG-box proteins Abf2 in yeast and TFAM in mammals are critical for mtDNA maintenance and packaging and have been linked to mtDNA copy number control. Here, we discover the previously unrecognized mitochondrial HMG-box protein Cim1 (copy number influence on mtDNA) in Saccharomyces cerevisiae, which exhibits metabolic state dependent mtDNA association. Surprisingly, in contrast to Abf2's supportive role in mtDNA maintenance, Cim1 negatively regulates mtDNA copy number. Cells lacking Cim1 display increased mtDNA levels and enhanced mitochondrial function, while Cim1 overexpression results in mtDNA loss. Intriguingly, Cim1 deletion alleviates mtDNA maintenance defects associated with loss of Abf2, while defects caused by Cim1 overexpression are mitigated by simultaneous overexpression of Abf2. Moreover, we find that the conserved LON protease Pim1 is essential to maintain low Cim1 levels, thereby preventing its accumulation and concomitant repressive effects on mtDNA. We propose a model in which the protein ratio of antagonistically acting Cim1 and Abf2 determines mtDNA copy number.
    MeSH term(s) Animals ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; HMGB Proteins/genetics ; HMGB Proteins/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances DNA, Mitochondrial ; HMGB Proteins ; Mitochondrial Proteins ; Saccharomyces cerevisiae Proteins ; ABF2 protein, S cerevisiae
    Language English
    Publishing date 2023-10-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad849
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    Zs.A 1067: Show issues Location:
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  2. Article ; Online: Yme2, a putative RNA recognition motif and AAA+ domain containing protein, genetically interacts with the mitochondrial protein export machinery.

    Sharma, Nupur / Osman, Christof

    Biological chemistry

    2022  Volume 403, Issue 8-9, Page(s) 807–817

    Abstract: The mitochondrial respiratory chain is composed of nuclear as well as mitochondrial-encoded subunits. A variety of factors mediate co-translational integration of mtDNA-encoded proteins into the inner membrane. ... ...

    Abstract The mitochondrial respiratory chain is composed of nuclear as well as mitochondrial-encoded subunits. A variety of factors mediate co-translational integration of mtDNA-encoded proteins into the inner membrane. In
    MeSH term(s) AAA Domain ; Electron Transport Complex IV/metabolism ; Membrane Proteins/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Nuclear Proteins/metabolism ; RNA Recognition Motif ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Electron Transport Complex IV (EC 1.9.3.1) ; MBA1 protein, S cerevisiae ; Membrane Proteins ; Mitochondrial Proteins ; Nuclear Proteins ; Saccharomyces cerevisiae Proteins ; YME2 protein, S cerevisiae
    Language English
    Publishing date 2022-01-31
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2021-0398
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  3. Book ; Online ; Thesis: Qualitätskontrolle der mitochondrialen DNA in S. cerevisiae

    Jakubke, Sean Christopher [Verfasser] / Osman, Christof [Akademischer Betreuer]

    2023  

    Author's details Sean Christopher Jakubke ; Betreuer: Christof Osman
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language German
    Publisher Universitätsbibliothek der Ludwig-Maximilians-Universität
    Publishing place München
    Document type Book ; Online ; Thesis
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  4. Book ; Online ; Thesis: Coordination of mitochondrial DNA homeostasis with cell growth

    Seel, Anika Vanessa [Verfasser] / Osman, Christof [Akademischer Betreuer]

    2022  

    Author's details Anika Vanessa Seel ; Betreuer: Christof Osman
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universitätsbibliothek der Ludwig-Maximilians-Universität
    Publishing place München
    Document type Book ; Online ; Thesis
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  5. Book ; Online ; Thesis: Defining childhood interstitial lung disease on the molecular level: Insights into known and novel genetic entities predisposing to fibrosis

    Schuch, Luise Antje [Verfasser] / Osman, Christof [Akademischer Betreuer]

    2022  

    Author's details Luise Antje Schuch ; Betreuer: Christof Osman
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universitätsbibliothek der Ludwig-Maximilians-Universität
    Publishing place München
    Document type Book ; Online ; Thesis
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  6. Article ; Online: An improved imaging system that corrects MS2-induced RNA destabilization.

    Li, Weihan / Maekiniemi, Anna / Sato, Hanae / Osman, Christof / Singer, Robert H

    Nature methods

    2022  Volume 19, Issue 12, Page(s) 1558–1562

    Abstract: The MS2 and MS2-coat protein (MS2-MCP) imaging system is widely used to study messenger RNA (mRNA) spatial distribution in living cells. Here, we report that the MS2-MCP system destabilizes some tagged mRNAs by activating the nonsense-mediated mRNA decay ...

    Abstract The MS2 and MS2-coat protein (MS2-MCP) imaging system is widely used to study messenger RNA (mRNA) spatial distribution in living cells. Here, we report that the MS2-MCP system destabilizes some tagged mRNAs by activating the nonsense-mediated mRNA decay pathway. We introduce an improved version, which counteracts this effect by increasing the efficiency of translation termination of the tagged mRNAs. Improved versions were developed for both yeast and mammalian systems.
    MeSH term(s) Animals ; Capsid Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Protein Biosynthesis ; Gene Expression Regulation ; RNA Stability ; Mammals/genetics
    Chemical Substances Capsid Proteins ; RNA, Messenger
    Language English
    Publishing date 2022-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-022-01658-1
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  7. Article ; Online: YeastMate: neural network-assisted segmentation of mating and budding events in Saccharomyces cerevisiae.

    Bunk, David / Moriasy, Julian / Thoma, Felix / Jakubke, Christopher / Osman, Christof / Hörl, David

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 9, Page(s) 2667–2669

    Abstract: Summary: Here, we introduce YeastMate, a user-friendly deep learning-based application for automated detection and segmentation of Saccharomyces cerevisiae cells and their mating and budding events in microscopy images. We build upon Mask R-CNN with a ... ...

    Abstract Summary: Here, we introduce YeastMate, a user-friendly deep learning-based application for automated detection and segmentation of Saccharomyces cerevisiae cells and their mating and budding events in microscopy images. We build upon Mask R-CNN with a custom segmentation head for the subclassification of mother and daughter cells during lifecycle transitions. YeastMate can be used directly as a Python library or through a standalone application with a graphical user interface (GUI) and a Fiji plugin as easy-to-use frontends.
    Availability and implementation: The source code for YeastMate is freely available at https://github.com/hoerlteam/YeastMate under the MIT license. We offer installers for our software stack for Windows, macOS and Linux. A detailed user guide is available at https://yeastmate.readthedocs.io.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Saccharomyces cerevisiae ; Software ; Microscopy ; Neural Networks, Computer ; Gene Library
    Language English
    Publishing date 2022-02-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac107
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    Zs.A 2374: Show issues Location:
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  8. Article ; Online: Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth.

    Seel, Anika / Padovani, Francesco / Mayer, Moritz / Finster, Alissa / Bureik, Daniela / Thoma, Felix / Osman, Christof / Klecker, Till / Schmoller, Kurt M

    Nature structural & molecular biology

    2023  Volume 30, Issue 10, Page(s) 1549–1560

    Abstract: To maintain stable DNA concentrations, proliferating cells need to coordinate DNA replication with cell growth. For nuclear DNA, eukaryotic cells achieve this by coupling DNA replication to cell-cycle progression, ensuring that DNA is doubled exactly ... ...

    Abstract To maintain stable DNA concentrations, proliferating cells need to coordinate DNA replication with cell growth. For nuclear DNA, eukaryotic cells achieve this by coupling DNA replication to cell-cycle progression, ensuring that DNA is doubled exactly once per cell cycle. By contrast, mitochondrial DNA replication is typically not strictly coupled to the cell cycle, leaving the open question of how cells maintain the correct amount of mitochondrial DNA during cell growth. Here, we show that in budding yeast, mitochondrial DNA copy number increases with cell volume, both in asynchronously cycling populations and during G1 arrest. Our findings suggest that cell-volume-dependent mitochondrial DNA maintenance is achieved through nuclear-encoded limiting factors, including the mitochondrial DNA polymerase Mip1 and the packaging factor Abf2, whose amount increases in proportion to cell volume. By directly linking mitochondrial DNA maintenance to nuclear protein synthesis and thus cell growth, constant mitochondrial DNA concentrations can be robustly maintained without a need for cell-cycle-dependent regulation.
    MeSH term(s) DNA, Mitochondrial/genetics ; Cell Cycle/genetics ; DNA Replication ; Homeostasis ; Cell Size
    Chemical Substances DNA, Mitochondrial
    Language English
    Publishing date 2023-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-023-01091-8
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    Zs.MG 56: Show issues

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  9. Article ; Online: Power to the daughters - mitochondrial and mtDNA transmission during cell division.

    Aretz, Ina / Jakubke, Christopher / Osman, Christof

    Biological chemistry

    2019  Volume 401, Issue 5, Page(s) 533–546

    Abstract: Mitochondria supply virtually all eukaryotic cells with energy through ATP production by oxidative phosphoryplation (OXPHOS). Accordingly, maintenance of mitochondrial function is fundamentally important to sustain cellular health and various diseases ... ...

    Abstract Mitochondria supply virtually all eukaryotic cells with energy through ATP production by oxidative phosphoryplation (OXPHOS). Accordingly, maintenance of mitochondrial function is fundamentally important to sustain cellular health and various diseases have been linked to mitochondrial dysfunction. Biogenesis of OXPHOS complexes crucially depends on mitochondrial DNA (mtDNA) that encodes essential subunits of the respiratory chain and is distributed in multiple copies throughout the mitochondrial network. During cell division, mitochondria, including mtDNA, need to be accurately apportioned to daughter cells. This process requires an intimate and coordinated interplay between the cell cycle, mitochondrial dynamics and the replication and distribution of mtDNA. Recent years have seen exciting advances in the elucidation of the mechanisms that facilitate these processes and essential key players have been identified. Moreover, segregation of qualitatively distinct mitochondria during asymmetric cell division is emerging as an important quality control step, which secures the maintenance of a healthy cell population.
    MeSH term(s) Animals ; Cell Division ; DNA, Mitochondrial/genetics ; Humans ; Mitochondria/metabolism
    Chemical Substances DNA, Mitochondrial
    Language English
    Publishing date 2019-11-27
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2019-0337
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  10. Article ; Online: Adaptive introgression of a visual preference gene.

    Rossi, Matteo / Hausmann, Alexander E / Alcami, Pepe / Moest, Markus / Roussou, Rodaria / Van Belleghem, Steven M / Wright, Daniel Shane / Kuo, Chi-Yun / Lozano-Urrego, Daniela / Maulana, Arif / Melo-Flórez, Lina / Rueda-Muñoz, Geraldine / McMahon, Saoirse / Linares, Mauricio / Osman, Christof / McMillan, W Owen / Pardo-Diaz, Carolina / Salazar, Camilo / Merrill, Richard M

    Science (New York, N.Y.)

    2024  Volume 383, Issue 6689, Page(s) 1368–1373

    Abstract: Visual preferences are important drivers of mate choice and sexual selection, but little is known of how they evolve at the genetic level. In this study, we took advantage of the diversity of bright warning patterns displayed ... ...

    Abstract Visual preferences are important drivers of mate choice and sexual selection, but little is known of how they evolve at the genetic level. In this study, we took advantage of the diversity of bright warning patterns displayed by
    MeSH term(s) Animals ; Female ; Butterflies/genetics ; Butterflies/physiology ; Calcium-Binding Proteins/genetics ; Color Vision/genetics ; Genes, Insect ; Genome ; Hybridization, Genetic ; Mating Preference, Animal ; Sexual Selection/genetics ; Genetic Introgression
    Chemical Substances Calcium-Binding Proteins
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adj9201
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