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Cristae undergo continuous cycles of fusion and fission in a MICOS-dependent manner

View ORCID ProfileArun Kumar Kondadi, View ORCID ProfileRuchika Anand, Sebastian Hänsch, View ORCID ProfileJennifer Urbach, Thomas Zobel, Dane M. Wolf, Mayuko Segawa, Marc Liesa, Orian S. Shirihai, Stefanie Weidtkamp-Peters, View ORCID ProfileAndreas S. Reichert
doi: https://doi.org/10.1101/654541
Arun Kumar Kondadi
1Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Ruchika Anand
1Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Sebastian Hänsch
2Center for Advanced Imaging, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Jennifer Urbach
1Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Thomas Zobel
2Center for Advanced Imaging, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Dane M. Wolf
3Department of Medicine, Nutrition and Metabolism Section, Evans Biomedical Research Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA
4Department of Medicine, Division of Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA
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Mayuko Segawa
4Department of Medicine, Division of Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA
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Marc Liesa
4Department of Medicine, Division of Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA
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Orian S. Shirihai
3Department of Medicine, Nutrition and Metabolism Section, Evans Biomedical Research Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA
4Department of Medicine, Division of Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA
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Stefanie Weidtkamp-Peters
2Center for Advanced Imaging, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Andreas S. Reichert
1Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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  • For correspondence: reichert@hhu.de
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Abstract

The mitochondrial inner membrane can reshape under different physiological conditions. How and at which frequency this occurs in vivo and what are the molecular players involved is unknown. Here we show using state-of-the-art live-cell stimulated emission depletion (STED) super-resolution nanoscopy that crista junctions (CJs) are dynamically fusing and dividing in a reversible and balanced manner at a timescale of seconds. CJ dynamics is strongly reduced in the absence of the MICOS subunit MIC13. Staining of the cristae membrane using different protein markers or two inner mitochondrial membrane-specific dyes revealed that cristae also undergo continuous cycles of fusion and fission. These processes are dependent on MIC13 and occur at a timescale of seconds, resembling CJ dynamics. Our data further suggest that MIC60 acts as a docking platform pioneering CJ formation. Overall, by employing a variety of advanced imaging techniques including FRAP (Fluorescence-Recovery-After Photobleaching), SPT (Single-Particle-Tracking), live-cell STED and confocal Airyscan microscopy we demonstrate that cristae undergo continuous cycles of fusion and fission in a manner that is mechanistically linked to CJ formation and dynamics.

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Posted May 30, 2019.
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Cristae undergo continuous cycles of fusion and fission in a MICOS-dependent manner
Arun Kumar Kondadi, Ruchika Anand, Sebastian Hänsch, Jennifer Urbach, Thomas Zobel, Dane M. Wolf, Mayuko Segawa, Marc Liesa, Orian S. Shirihai, Stefanie Weidtkamp-Peters, Andreas S. Reichert
bioRxiv 654541; doi: https://doi.org/10.1101/654541
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Cristae undergo continuous cycles of fusion and fission in a MICOS-dependent manner
Arun Kumar Kondadi, Ruchika Anand, Sebastian Hänsch, Jennifer Urbach, Thomas Zobel, Dane M. Wolf, Mayuko Segawa, Marc Liesa, Orian S. Shirihai, Stefanie Weidtkamp-Peters, Andreas S. Reichert
bioRxiv 654541; doi: https://doi.org/10.1101/654541

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