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Mol. Biol. Cell Sep (2006); 17(9):3756-67
The novel F-box protein Mfb1p regulates mitochondrial connectivity and exhibits asymmetric localization in yeast-
Kondo-Okamoto N, Ohkuni K, Kitagawa K, McCaffery JM, Shaw JM, Okamoto K
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA-
Abstract: Although it is clear that mitochondrial morphogenesis is a complex process involving multiple proteins in eukaryotic cells, little is known about regulatory molecules that modulate mitochondrial network formation- Here, we report the identification of a new yeast mitochondrial morphology gene called MFB1 -YDR219C-- MFB1 encodes an F-box protein family member, many of which function in Skp1-Cdc53-Cullin-F-box protein -SCF- ubiquitin ligase complexes- F-box proteins also act in non-SCF complexes whose functions are not well understood- Although cells lacking Mfb1p contain abnormally short mitochondrial tubules, Mfb1p is not essential for known pathways that determine mitochondrial morphology and dynamics- Mfb1p is peripherally associated with the mitochondrial surface- Coimmunoprecipitation assays reveal that Mfb1p interacts with Skp1p in an F-box-dependent manner- However, Mfb1p does not coimmunoprecipitate with Cdc53p- The F-box motif is not essential for Mfb1p-mediated mitochondrial network formation- These observations suggest that Mfb1p acts in a complex lacking Cdc53p required for mitochondrial morphogenesis- During budding, Mfb1p asymmetrically localizes to mother cell mitochondria- By contrast, Skp1p accumulates in the daughter cell cytoplasm- Mfb1p mother cell-specific asymmetry depends on the F-box motif, suggesting that Skp1p down-regulates Mfb1p mitochondrial association in buds- We propose that Mfb1p operates in a novel pathway regulating mitochondrial tubular connectivity-
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Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.