title: Cdc48p/p97-mediated regulation of mitochondrial morphology is Vms1p-independent.
abstract: Cdc48p/p97 is a cytosolic essential AAA chaperone, which regulates multiple cellular reactions in a ubiquitin-dependent manner. We have recently shown that Cdc48p exhibits positively cooperative ATPase activity and loss of the positive cooperativity results in yeast cell death. Here we show that loss of the positive cooperativity of the yeast Cdc48p ATPase activity led to severe mitochondrial aggregation. The actin cytoskeleton and distribution of the ER-mitochondria tethering complex (ERMES) were eliminated from the cause of the mitochondrial aggregation. Instead, a mitochondrial outer membrane protein Fzo1p, which is required for mitochondrial fusion, and components of ERMES, which is involved in mitochondrial morphology, were remarkably stabilized in the Cdc48p mutants. In the last couple of years, it was shown that Vms1p functions as a cofactor of Cdc48p for the function of protein degradation of mitochondrial outer membrane proteins. Nevertheless, we found that Vms1p was not involved in the Cdc48p-dependent mitochondrial aggregation and loss of Vms1p did not significantly affect degradation rates of proteins anchored to the mitochondrial outer membrane. These results suggest that Cdc48p controls mitochondrial morphology by regulating turnover of proteins involved in mitochondrial morphology in a Vms1p-independent manner.
authors.affiliation: Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan. esaki@kumamoto-u.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Esaki
authors.forename: Teru
authors.initials: T
authors.lastname: Ogura
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation / Q000235:genetics / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000074405:Valosin Containing Protein
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; C557318:Vms1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein