title: STED super-resolution microscopy reveals an array of MINOS clusters along human mitochondria.
abstract: The mitochondrial inner membrane organizing system (MINOS) is a conserved large hetero-oligomeric protein complex in the mitochondrial inner membrane, crucial for the maintenance of cristae morphology. MINOS has been suggested to represent the core of an extended protein network that controls mitochondrial function and structure, and has been linked to several human diseases. The spatial arrangement of MINOS within mitochondria is ill-defined, however. Using super-resolution stimulated emission depletion (STED) microscopy and immunogold electron microscopy, we determined the distribution of three known human MINOS subunits (mitofilin, MINOS1, and CHCHD3) in mammalian cells. Super-resolution microscopy revealed that all three subunits form similar clusters within mitochondria, and that MINOS is more abundant in mitochondria around the nucleus than in peripheral mitochondria. At the submitochondrial level, mitofilin, a core MINOS subunit, is preferentially localized at cristae junctions. In primary human fibroblasts, mitofilin labeling uncovered a regularly spaced pattern of clusters arranged in parallel to the cell growth surfaces. We suggest that this array of MINOS complexes might explain the observed phenomenon of largely horizontally arranged cristae junctions that connect the inner boundary membrane to lamellar cristae. The super-resolution images demonstrate an unexpectedly high level of regularity in the nanoscale distribution of the MINOS complex in human mitochondria, supporting an integrating role of MINOS in the structural organization of the organelle.
authors.affiliation: Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Jans
authors.forename: Christian A
authors.initials: CA
authors.lastname: Wurm
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.forename: Dirk
authors.initials: D
authors.lastname: Wenzel
authors.forename: Franziska
authors.initials: F
authors.lastname: Stagge
authors.forename: Markus
authors.initials: M
authors.lastname: Deckers
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Stefan
authors.initials: S
authors.lastname: Jakobs
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence / Q000379:methods*; D016253:Microscopy, Immunoelectron; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D036103:Nanotechnology; D012441:Saccharomyces cerevisiae; D014709:Vero Cells
chemical_list: C088548:IMMT protein, human; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins
keywords: MICOS; MitOS; membrane architecture; nanoscopy