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ERC

MitoShape Report Summary

Project ID: 616024
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - MITOSHAPE (Structural basis of mitochondrial inner membrane shape and dynamic)

In the ERC project MitoShape, my group explores the structure and mechanisms of cellular machineries mediating the shape of mitochondria, which are the powerhouses of the cell. For example, they produce ATP, a major energy carrier in cells, and many cellular building blocks. In addition, mitochondria are involved in numerous other functions essential for the viability of the cell. Not surprisingly, mitochondrial dysfunction leads to severe disease, such as neurodegeneration and cancer.
Mitochondria have a tubular double membrane architecture: the inner mitochondrial membrane is divided into the inner boundary membrane, which aligns with the outer membrane, and membrane invaginations called cristae. The inner boundary membrane and cristae are connected by tubular openings, the crista junctions. Mitochondrial shape constantly changes due to membrane fission and fusion events, and a balance of both processes is required for proper functioning of mitochondria.
In WP 1, my group explores the OPA1 protein, a mechano-chemical enzyme previously shown to be involved in the remodeling of mitochondrial membranes. We want to determine the 3-dimensinal structure of OPA1 to understand the mechanism how it remodels membranes. Results of this working package may help us to understand the molecular basis of Optic atrophy type1, a neurodegenerative disease of the eye, which can be caused by mutations in OPA1.
A multiprotein complex called MICOS was recently shown to be involved in the formation of crista junctions. We are interested to study the three dimensional structure of MICOS to understand how it fulfills its function in mitochondrial architecture. We could recently show that one of its subunits, Mic60, binds directly to membranes leading to their remodeling. Membrane remodeling of Mic60 is supported by a second subunit, Mic19. This suggests a novel, unexpected function of Mic60 in shaping mitochondria. We will continue our efforts to characterize the structural mechanisms underlying this process.
In the final working package, we want to study the molecular basis of how the MICOS complex is integrated into a mitochondrial network of proteins. We therefore seek to study previously described interactions of MICOS, for example with the OPA1 GTPase. This will results in a complete picture of how MICOS carries out its function in the mitochondrial environment.

Reported by

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN
Germany
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