title: Mitochondrial Fragmentation Due to Inhibition of Fusion Increases Cyclin B through Mitochondrial Superoxide Radicals.
abstract: During the cell cycle, mitochondria undergo regulated changes in morphology. Two particularly interesting events are first, mitochondrial hyperfusion during the G(1)-S transition and second, fragmentation during entry into mitosis. The mitochondria remain fragmented between late G(2)- and mitotic exit. This mitotic mitochondrial fragmentation constitutes a checkpoint in some cell types, of which little is known. We bypass the 'mitotic mitochondrial fragmentation' checkpoint by inducing fragmented mitochondrial morphology and then measure the effect on cell cycle progression. Using Drosophila larval hemocytes, Drosophila S2R(+) cell and cells in the pouch region of wing imaginal disc of Drosophila larvae we show that inhibiting mitochondrial fusion, thereby increasing fragmentation, causes cellular hyperproliferation and an increase in mitotic index. However, mitochondrial fragmentation due to over-expression of the mitochondrial fission machinery does not cause these changes. Our experiments suggest that the inhibition of mitochondrial fusion increases superoxide radical content and leads to the upregulation of cyclin B that culminates in the observed changes in the cell cycle. We provide evidence for the importance of mitochondrial superoxide in this process. Our results provide an insight into the need for mitofusin-degradation during mitosis and also help in understanding the mechanism by which mitofusins may function as tumor suppressors.
authors.affiliation: National Centre for Biological Sciences (NCBS-TIFR), UAS-GKVK campus, Bellary road, Bangalore, 560 065, Karnataka, India; inStem, Institute for Stem Cell Biology and Regenerative Medicine, GKVK post, Bellary road, Bangalore, 560 065, Karnataka, India.
authors.forename: Tejas M
authors.initials: TM
authors.lastname: Gupte
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D019926:Cyclin B / Q000378:metabolism*; D004330:Drosophila; D005434:Flow Cytometry; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000235:genetics / Q000502:physiology; D008940:Mitotic Index; D013481:Superoxides / Q000378:metabolism*
chemical_list: D019926:Cyclin B; D013481:Superoxides