Abstracts
Visualizing the structure and dynamics of mitochondria at the nanoscale
Till Stephan
Buchmann Institute for Molecular Life Sciences - BMLS, Goethe University Frankfurt, Max-von-Laue-Straße 15, Frankfurt am Main, 60438, Germany
Mitochondria, often referred to as the powerhouses of the cell, are vital for maintaining cellular homeostasis. Their unique double-membrane structure is intricately linked to their metabolic functions. The smooth outer membrane encases the inner membrane, which forms cristae—invaginations that house the protein machinery essential for ATP synthesis. Alterations in mitochondrial ultrastructure are implicated in various severe human diseases, including neurodegenerative disorders and myopathies. However, understanding cristae formation has been challenging due to the lack of technologies capable of resolving mitochondrial ultrastructure in live cells.
In this presentation, I will discuss recent advancements that have enabled live-cell super-resolution microscopy recordings of mitochondrial cristae. These recordings reveal the highly dynamic nature of mitochondrial cristae, which undergo rapid remodeling on a timescale of seconds. By integrating data from live-cell STED microscopy, single-molecule localization microscopy, 3D electron microscopy, and biochemical approaches, we have gained valuable new insights into the function of mitochondrial membrane-shaping protein complexes and their role in cristae formation.
Literature:
Stephan T, Stoldt S, Barbot M, Carney TD, Lange F, Bates M, Bou Dib P, Inamdar K, Shcherbata HR, Meinecke M, Riedel D, Dennerlein S, Rehling P, Jakobs S. Drosophila MIC10b can polymerize into cristae-shaping filaments. Life Sci Alliance. 2024 Jan 22;7(4):e202302177. doi: 10.26508/lsa.202302177. PMID: 38253420; PMCID: PMC10803214.
Chen J, Stephan T, Gaedke F, Liu T, Li Y, Schauss A, Chen P, Wulff V, Jakobs S, Jüngst C, Chen Z. An aldehyde-crosslinking mitochondrial probe for STED imaging in fixed cells. Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2317703121. doi: 10.1073/pnas.2317703121. Epub 2024 Apr 30. PMID: 38687792; PMCID: PMC11087744.
Liu T, Stephan T, Chen P, Keller-Findeisen J, Chen J, Riedel D, Yang Z, Jakobs S, Chen Z. Multi-color live-cell STED nanoscopy of mitochondria with a gentle inner membrane stain. Proc Natl Acad Sci U S A. 2022 Dec 27;119(52):e2215799119. doi: 10.1073/pnas.2215799119. Epub 2022 Dec 19. PMID: 36534799; PMCID: PMC9907107.
Stephan T, Brüser C, Deckers M, Steyer AM, Balzarotti F, Barbot M, Behr TS, Heim G, Hübner W, Ilgen P, Lange F, Pacheu-Grau D, Pape JK, Stoldt S, Huser T, Hell SW, Möbius W, Rehling P, Riedel D, Jakobs S. MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. EMBO J. 2020 Jul 15;39(14):e104105. doi: 10.15252/embj.2019104105. Epub 2020 Jun 22. PMID: 32567732; PMCID: PMC7361284.