Project 20

Cholesterol transfer at ER-mitochondria contact sites and its impact on mitochondrial function

Principle Investigator: Dr. Till Stephan

Research Areas: Cell Biology, Membrane Biology

Summary

The cholesterol content of mitochondria influences their function and steroid hormone synthesis, yet the mechanisms governing the subcellular transport of cholesterol and steroids remain insufficiently understood. This project investigates how lipid transfer proteins regulate the exchange of cholesterol and pregnenolone both between the outer and inner mitochondrial membrane and at ER–mitochondria contact sites. Using modern super-resolution microscopy, lipidomics, and functional analyses, we aim to gain new insights into mechanisms of sterol and steroid transport in cellulo.

Dr. Till Stephan

Goethe University Frankfurt Website

: PROJECT-RELATED PUBLICATIONS

  1. Preminger N, Zucker B, Hassdenteufel S, Stephan T, Jakobs S, Kozlov MM*, Schuldiner M* (2025) A data-driven model for mitochondrial inner membrane remodeling as a driving force of organelle shaping. J Cell Sci 138, jcs263850
  2. Stephan T#, Stoldt S#, Barbot M#, Carney TD, Lange F, Bates M, Bou Dib P, Inamdar K, Shcherbata HR, Meinecke M, et al (2024) Drosophila MIC10b can polymerize into cristae-shaping filaments. Life Sci Alliance 7, e202302177
  3. Chen J, Stephan T, Gaedke F, Liu T, Li Y, Schauss A, Chen P, Wulff V, Jakobs S, Jüngst C*, Chen Z* (2024) An aldehyde-crosslinking mitochondrial probe for STED imaging in fixed cells. Proc Natl Acad Sci USA 121, e2317703121
  4. Ebrahimi V, Stephan T, Kim J, Carravilla P, Eggeling C, Jakobs S, Han KY* (2023) Deep learning enables fast, gentle STED microscopy. Commun Biol 6, 674
  5. Liu T#, Stephan T#, Chen P, Keller-Findeisen J, Chen J, Riedel D, Yang Z, Jakobs S, Chen Z* (2022) Multi-color live-cell STED nanoscopy of mitochondria with a gentle inner membrane stain. Proc Natl Acad Sci USA 119, e2215799119 
  6. Bates M*, Keller-Findeisen J, Przybylski A, Hüper A, Stephan T, Ilgen P, Cereceda Delgado AR, D’Este E, Egner A, Jakobs S, Sahl SJ, Hell SW* (2022) Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models. Nat Methods 19, 603–612. doi:10.1038/s41592-022-01465-8 
  7. Tameling C, Stoldt S, Stephan T, Naas J, Jakobs S, Munk A* (2021) Colocalization for super-resolution microscopy via optimal transport. Nat Comput Sci 1, 199–211
  8. 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* (2020) MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. EMBO J 39, e104105
  9. Pape JK#, Stephan T#, Balzarotti F, Büchner R, Lange F, Riedel D, Jakobs S*, Hell SW* (2020) Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins. Proc Natl Acad Sci USA 117, 20607–20614
  10. Stephan T, Rösch A, Riedel D, Jakobs S* (2019) Live-cell STED nanoscopy of mitochondrial cristae. Sci Rep 9, 12419
*corresponding author; #shared first author