Mechanisms of Mitochondrial Fusion and Fission

Citation

Griffin, Erik Edmund (2006) Mechanisms of Mitochondrial Fusion and Fission. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/902F-8M09. https://resolver.caltech.edu/CaltechETD:etd-05242006-134647

Abstract

We have studied the mechanisms of mitochondrial fusion and fission in S. cerevisiae. Using a proteomics-based approach, we have identified the WD domain protein Caf4p as a Fis1p binding partner that, along with its paralog Mdv1p, functions as a molecular adaptor between Fis1p and Dnm1p. This work defines a role for Mdv1p and Caf4p in the recruitment of Dnm1p to mitochondrial fission complexes. In a separate study, we focus on the role of Fzo1p during mitochondrial fusion. Fzo1p and its mammalian homologs, Mfn1 and Mfn2, are conserved transmembrane GTPases that are required for mitochondrial fusion. A structure/function analysis has established an essential role for three Fzo1p heptad repeat regions during mitochondrial fusion. Furthermore, we show that Fzo1p functions as an oligomer and forms critical interactions between the HRN/GTPase and HR1/HR2 regions. Finally, we have identified Om14p as a novel regulator of mitochondrial morphology. Om14p interacts with Fzo1p and Ugo1p and may be the first inhibitor of mitochondrial fusio

Thesis Files