title: Regulation of mitochondrial morphology by USP30, a deubiquitinating enzyme present in the mitochondrial outer membrane.
abstract: Recent studies have suggested that ubiquitination of mitochondrial proteins participates in regulating mitochondrial dynamics in mammalian cells, but it is unclear whether deubiquitination is involved in this process. Here, we identify human ubiquitin-specific protease 30 (USP30) as a deubiquitinating enzyme that is embedded in the mitochondrial outer membrane. Depletion of USP30 expression by RNA interference induced elongated and interconnected mitochondria, depending on the activities of the mitochondrial fusion factors mitofusins, without changing the expression levels of the key regulators for mitochondrial dynamics. Mitochondria were rescued from this abnormal phenotype by ectopic expression of USP30 in a manner dependent on its enzymatic activity. Our findings reveal that USP30 participates in the maintenance of mitochondrial morphology, a finding that provides new insight into the cellular function of deubiquitination.
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan. nnakamur@bio.titech.ac.jp
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakamura
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Hirose
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D053140:Organelle Shape; D010802:Phylogeny; D021382:Protein Sorting Signals; D021381:Protein Transport; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; C532819:Usp30 protein, human; D013869:Thiolester Hydrolases; D010450:Endopeptidases