Project Details
Projekt
Molecular characterization of protein-dependent inner mitochondrial membrane morphogenesis
Applicant
Professor Dr. Michael Meinecke
Subject Area
Cell Biology
Biochemistry
Biophysics
Biochemistry
Biophysics
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 401510699
One of the morphology defining elements of the inner mitochondrial membrane are cristae junctions (CJs). These membrane segments display high degrees of membrane curvature and connect inner boundary membranes with cristae membranes. The multi-subunit MICOS complex is required to maintain and probably form cristae junctions. MICOS consists of proteins with the ability to bend membranes and to form extensive protein-protein interaction networks. While some progress has been made in attributing specific functions to single MICOS subunits a detailed understanding of how the various complex proteins act in a concerted manner but also with other proteins and with lipids is largely missing. We will use complementary biochemical, biophysical and cell biological approaches to unravel the role of MICOS as a membrane shaping and organizing hub at a molecular level. As a first aim, we will reconstitute the minimal MICOS network required for membrane shaping and membrane contact site formation. Various model membrane systems together with purified proteins will be employed to first reconstitute MICOS dependent membrane bridging. In a second step these structures will be used to co-reconstitute membrane bridging and MICOS dependent membrane remodeling within the same system. Results from this part of the project will unravel the minimal unit that establishes membrane contact sites and cristae organization, the two main function of MICOS. For the second aim we will take a step closer towards a detailed molecular understanding of intra-mitochondrial lipid transfer. We were able to show a membrane morphology dependency of mitochondrial lipid transfer proteins and will now, besides investigate this effect in more detail, analyze how these proteins work in the context of the different MICOS functions and other inner membrane scaffolding proteins. Together we aim to achieve a better understanding of inner membrane morphogenesis and how it affects important physiological processes.
DFG Programme
Research Units
