A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics.
In this study, we have identified a novel mitochondrial ubiquitin ligase, designated MITOL, which is localized in the mitochondrial outer membrane. MITOL possesses a Plant Homeo-Domain (PHD) motif responsible for E3 ubiquitin ligase activity and predicted four-transmembrane domains. MITOL displayed a rapid degradation by autoubiquitination activity in a PHD-dependent manner. ... HeLa cells stably expressing a MITOL mutant lacking ubiquitin ligase activity or MITOL-deficient cells by small interfering RNA showed an aberrant mitochondrial morphology such as fragmentation, suggesting the enhancement of mitochondrial fission by MITOL dysfunction. Indeed, a dominant-negative expression of Drp1 mutant blocked mitochondrial fragmentation induced by MITOL depletion. We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1. Pulse-chase experiment showed that MITOL overexpression increased turnover of these fission proteins. In addition, overexpression phenotype of hFis1 could be reverted by MITOL co-overexpression. Our finding indicates that MITOL plays a critical role in mitochondrial dynamics through the control of mitochondrial fission proteins.
Mesh Terms:
Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Down-Regulation, HeLa Cells, Humans, Intracellular Membranes, Microscopy, Fluorescence, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Ubiquitin-Protein Ligases
Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Down-Regulation, HeLa Cells, Humans, Intracellular Membranes, Microscopy, Fluorescence, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Ubiquitin-Protein Ligases
EMBO J.
Date: Aug. 09, 2006
PubMed ID: 16874301
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