Deletion of a novel F-box protein, MUS-10, in Neurospora crassa leads to altered mitochondrial morphology, instability of mtDNA and senescence.
While mitochondria are renowned for their role in energy production, they also perform several other integral functions within the cell. Thus, it is not surprising that mitochondrial dysfunction can negatively impact cell viability. Although mitochondria have received an increasing amount of attention in recent years, there is still relatively little information about how proper maintenance of mitochondria and its genomes is achieved. The Neurospora crassa mus-10 mutant was first identified through its increased sensitivity to methyl methanesulfonate (MMS) and was thus believed to be defective in some aspect of DNA repair. Here, we report that mus-10 harbors fragmented mitochondria and that it accumulates deletions in its mitochondrial DNA (mtDNA), suggesting that the mus-10 gene product is involved in mitochondrial maintenance. Interestingly, mus-10 begins to senesce shortly after deletions are visualized in its mtDNA. To uncover the function of MUS-10, we used a gene rescue approach to clone the mus-10 gene and discovered that it encodes a novel F-box protein. We show that MUS-10 interacts with a core component of the Skp, Cullin, F-box containing (SCF) complex, SCON-3, and that its F-box domain is essential for its function in vivo. Thus, we provide evidence that MUS-10 is part of an E3 ubiquitin ligase complex involved in maintaining the integrity of mitochondria and may function to prevent cellular senescence.
Laboratory of Genetics, Department of Regulatory Biology, Faculty of Science, Saitama University, Saitama 338-8570, Japan.
Akihiro
A
Kato
Kiminori
K
Kurashima
Michael
M
Chae
Satoshi
S
Sawada
Shin
S
Hatakeyama
Shuuitsu
S
Tanaka
Hirokazu
H
Inoue
D001483:Base Sequence; D015153:Blotting, Western; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D044782:F-Box Motifs / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D025301:Hyphae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009492:Neurospora crassa / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011485:Protein Binding; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020798:Two-Hybrid System Techniques
D044842:Cullin Proteins; D004272:DNA, Mitochondrial; D044783:F-Box Proteins; D005656:Fungal Proteins; D044786:S-Phase Kinase-Associated Proteins