Translocation of SenP5 from the nucleoli to the mitochondria modulates DRP1-dependent fission during mitosis.
The mechanisms that ensure an equal inheritance of cellular organelles during mitosis are an important area of study in cell biology. For the mitochondria fragment during mitosis, however, the cellular links that signal these changes are largely unknown. We recently identified a SUMO protease, SenP5, that deSUMOylates a number of mitochondrial targets, including the dynamin-related fission GTPase, DRP1. In interphase, SenP5 resides primarily within the nucleoli, in addition to a cytosolic pool. Here we report the relocalization of SenP5 from the nucleoli to the mitochondrial surface at G2/M transition prior to nuclear envelope breakdown. The recruitment of SenP5 results in a significant loss in mitochondrial SUMOylation, and a concomitant increase in the labile pool of DRP1 that drives mitochondrial fragmentation. Importantly, silencing of SenP5 leads to an arrest in the cell cycle precisely at the time when the protease is translocated to the mitochondria. These data indicate that transition of SenP5 to the mitochondria plays an important role in mitochondrial fragmentation during mitosis. The altered intracellular localization of SenP5 represents the first example of the mitochondrial recruitment of a SUMO protease and provides new insights into the mechanisms of interorganellar communication during the cell cycle.
University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.
Rodolfo
R
Zunino
Emélie
E
Braschi
Liqun
L
Xu
Heidi M
HM
McBride
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D019556:COS Cells; D002453:Cell Cycle; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D034281:Dynamins; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000494:pharmacology; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; D010447:Peptide Hydrolases; C512579:Senp5 protein, human; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins