title: Ablation of the single dynamin of T. brucei blocks mitochondrial fission and endocytosis and leads to a precise cytokinesis arrest.
abstract: Mitochondrial fission is mediated by dynamin-like proteins (DLPs). Trypanosoma brucei contains a single DLP, which is the only member of the dynamin superfamily. We have previously shown that expression of the human proapoptotic Bax in T. brucei induces extensive mitochondrial fragmentation. Here we report that Baxinduced mitochondrial fission is abolished in cell lines lacking functional DLP suggesting that the protein is also required for mitochondrial division during the cell cycle. Furthermore, DLP-ablated cells are deficient for endocytosis and as a consequence accumulate enlarged flagellar pockets. Thus, besides its expected role in mitochondrial fission the trypanosomal DLP is required for endocytosis, a function thought to be restricted to classical dynamins. In agreement with its dual function, the DLP localizes to both the mitochondrion and the flagellar pocket, the site where endocytosis occurs. Unexpectedly, ablation of DLP also causes an arrest of cytokinesis. The fact that no multinucleation is observed in the arrested cells argues for a precise cell-cycle block. Furthermore, analysis of a clathrin-knockdown cell line suggests that the cytokinesis arrest is not due to the endocytosis defect. Thus, our results support a working model in which mitochondrial fission triggers a checkpoint for cytokinesis.
authors.affiliation: Department of Biology/Cell and Developmental Biology, University of Fribourg, Chemin du Musée 10, CH-1700 Fribourg, Switzerland.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Chanez
authors.forename: Adrian B
authors.initials: AB
authors.lastname: Hehl
authors.forename: Markus
authors.initials: M
authors.lastname: Engstler
authors.forename: André
authors.initials: A
authors.lastname: Schneider
mesh_terms: D000818:Animals; D048749:Cytokinesis; D034281:Dynamins / Q000172:deficiency* / Q000235:genetics; D004705:Endocytosis; D005407:Flagella / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D021381:Protein Transport; D034622:RNA Interference; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D034281:Dynamins