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      Regulation of mitochondrial proteostasis by the proton gradient


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          Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multiproteomic approach to demonstrate the regulation of the m‐AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca 2+/H + exchanger in the mitochondrial inner membrane, which binds to and inhibits the m‐AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca 2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m‐AAA protease. The m‐AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca 2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.


          TMBIM5‐driven Ca 2+/H + exchange couples mitochondrial protein turnover to energetic status and metabolism.

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          NIH Image to ImageJ: 25 years of image analysis

          For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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            MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.

            Efficient analysis of very large amounts of raw data for peptide identification and protein quantification is a principal challenge in mass spectrometry (MS)-based proteomics. Here we describe MaxQuant, an integrated suite of algorithms specifically developed for high-resolution, quantitative MS data. Using correlation analysis and graph theory, MaxQuant detects peaks, isotope clusters and stable amino acid isotope-labeled (SILAC) peptide pairs as three-dimensional objects in m/z, elution time and signal intensity space. By integrating multiple mass measurements and correcting for linear and nonlinear mass offsets, we achieve mass accuracy in the p.p.b. range, a sixfold increase over standard techniques. We increase the proportion of identified fragmentation spectra to 73% for SILAC peptide pairs via unambiguous assignment of isotope and missed-cleavage state and individual mass precision. MaxQuant automatically quantifies several hundred thousand peptides per SILAC-proteome experiment and allows statistically robust identification and quantification of >4,000 proteins in mammalian cell lysates.
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              The Perseus computational platform for comprehensive analysis of (prote)omics data.

              A main bottleneck in proteomics is the downstream biological analysis of highly multivariate quantitative protein abundance data generated using mass-spectrometry-based analysis. We developed the Perseus software platform (http://www.perseus-framework.org) to support biological and biomedical researchers in interpreting protein quantification, interaction and post-translational modification data. Perseus contains a comprehensive portfolio of statistical tools for high-dimensional omics data analysis covering normalization, pattern recognition, time-series analysis, cross-omics comparisons and multiple-hypothesis testing. A machine learning module supports the classification and validation of patient groups for diagnosis and prognosis, and it also detects predictive protein signatures. Central to Perseus is a user-friendly, interactive workflow environment that provides complete documentation of computational methods used in a publication. All activities in Perseus are realized as plugins, and users can extend the software by programming their own, which can be shared through a plugin store. We anticipate that Perseus's arsenal of algorithms and its intuitive usability will empower interdisciplinary analysis of complex large data sets.

                Author and article information

                EMBO J
                EMBO J
                The EMBO Journal
                John Wiley and Sons Inc. (Hoboken )
                01 August 2022
                August 2022
                01 August 2022
                : 41
                : 16 ( doiID: 10.1002/embj.v41.16 )
                : e110476
                [ 1 ] Max Planck Institute for Biology of Ageing Cologne Germany
                [ 2 ] Department of Cellular Biochemistry University Medical Center Göttingen Göttingen Germany
                [ 3 ] Heidelberg University Biochemistry Center (BZH) Heidelberg Germany
                [ 4 ] Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands
                [ 5 ] Cologne Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne Cologne Germany
                [ 6 ] Institute for Genetics University of Cologne Cologne Germany
                Author notes
                [*] [* ]Corresponding author. Tel: +49 221 379 70 500; E‐mail: tlanger@ 123456age.mpg.de
                Author information
                © 2022 The Authors. Published under the terms of the CC BY 4.0 license

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                : 29 June 2022
                : 17 December 2021
                : 01 July 2022
                Page count
                Figures: 14, Tables: 1, Pages: 24, Words: 20160
                Funded by: Deutsche Forschungsgemeinschaft (DFG)
                Award ID: FOR2848
                Award ID: RA1028/10‐2
                Award ID: CRC1218‐269925409
                Funded by: EC ¦ Horizon 2020 Framework Programme (H2020) , doi 10.13039/100010661;
                Award ID: 721757
                Funded by: European Molecular Biology Organization (EMBO) , doi 10.13039/100004410;
                Award ID: ALTF649‐2015
                Award ID: ALTF 649‐2015
                Award ID: LTFCOFUND2013
                Award ID: GA‐2013‐609409
                Funded by: MEXT ¦ Japan Society for the Promotion of Science (JSPS)
                Award ID: ‐‐
                Funded by: The Osamu Hayaishi Memorial Scholarship for Study Abroad
                Funded by: Uehara Memorial Foundation (#x4e0a;xxx539F;xxx8A18;#x5ff5;#x751f;#x547d;#x79D1;#x5b66;xxx8CA1;xxx56E3;) , doi 10.13039/100008732;
                Funded by: ZonMw (Netherlands Organisation for Health Research and Development) , doi 10.13039/501100001826;
                Award ID: TOP714.017.00 4
                Custom metadata
                16 August 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:16.08.2022

                Molecular biology
                afg3l2,mitochondrial calcium,proton gradient,respiratory chain,tmbim5,membranes & trafficking,metabolism,post-translational modifications & proteolysis


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