Regulation of mitochondrial morphology through proteolysis of the mitofusin Fzo1 in the outer membrane

• Applicant: Dr. Mafalda Escobar-Henriques
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2007 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 41161362

Mitochondrial morphology is dynamically maintained by continuously occurring fusion and fission events. Such plasticity is essential for a correct energetic balance and for development but also contributes to apoptosis. Nevertheless, the regulation of fusion mechanisms is barely understood. Our recent findings in Saccharomyces cerevisiae have revealed that mitochondria! fusion is controlled by degradation of a central component, the highly conserved outer membrane protein Fzo1. These studies have started to unravel the degradation mechanisms for outer membrane proteins, for long unknown. Two pathways -ubiquitin proteasome dependent and independent- to that contribute to degradation of the mitofusin Fzo1 were revealed. We want to further understand the regulatory role of proteolysis for mitochondrial fusion and address the general problem of outer membrane protein turnover. We will employ genetic and biochemical approaches on both Fzo1 and genetically engineered model substrates. Such studies should open new perspectives into the general mechanisms guiding turnover of proteins in cellular membranes.

• DFG Programme: Research Grants