The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission.
Yeast mitochondrial fission is a multistep process during which the dynamin-related GTPase, Dnm1p, assembles into punctate structures that associate with the outer mitochondrial membrane and mediate mitochondrial division. Steps in the Dnm1p-dependent process of fission are regulated by the actions of the WD repeat protein, Mdv1p, and the mitochondrial outer membrane protein, Fis1p. Our previous studies suggested a model where Mdv1p functions to regulate fission at a post-Dnm1p assembly step and Fis1p functions at two distinct steps, at an early point, to regulate Dnm1p assembly, and later, together with Mdv1p, to facilitate Dnm1p-dependent mitochondrial fission. To test this model, we have examined the physical and functional relationship between Mdv1p and Fis1p and present genetic, biochemical, and two-hybrid data indicating that a Fis1p-Mdv1p complex is required to regulate mitochondrial fission. To further define the role of Mdv1p in fission, we examined the structural features of Mdv1p required for its interactions with Dnm1p and Fis1p. Data from two-hybrid analyses and GFP-tagged domains of Mdv1p indicate that it contains two functionally distinct domains that enable it to function as a molecular adaptor to regulate sequential interactions between Dnm1p and Fis1p and catalyze a rate-limiting step in mitochondrial fission.
Tieu
Quinton
Q
Section of Molecular and Cellular Biology, University of California, Davis, 95616, USA.
Okreglak
Voytek
V
Naylor
Kari
K
Nunnari
Jodi
J
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D034982:Integration Host Factors; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D046911:Macromolecular Substances; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C464859:FIS1 protein, S cerevisiae; D005656:Fungal Proteins; D034982:Integration Host Factors; C429283:MDV1 protein, S cerevisiae; D046911:Macromolecular Substances; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D020558:GTP Phosphohydrolases; C094774:DNM1 protein, S cerevisiae