title: Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA.
abstract: Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS). At the cellular level, mitochondrial dysfunction resulting from the lack of fission leads to a drop in the levels of cellular ATP, an inhibition of cell proliferation and an increase in autophagy. In conclusion, we propose that mitochondrial fission is required for preservation of mitochondrial function and thereby for maintenance of cellular homeostasis.
authors.affiliation: Department of Cell Biology, University of Geneva, Geneva, Switzerland.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Parone
authors.forename: Sandrine
authors.initials: S
authors.lastname: Da Cruz
authors.forename: Daniel
authors.initials: D
authors.lastname: Tondera
authors.forename: Yves
authors.initials: Y
authors.lastname: Mattenberger
authors.forename: Dominic I
authors.initials: DI
authors.lastname: James
authors.forename: Pierre
authors.initials: P
authors.lastname: Maechler
authors.forename: François
authors.initials: F
authors.lastname: Barja
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001343:Autophagy; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000378:metabolism*; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D010101:Oxygen Consumption; D034622:RNA Interference; D017382:Reactive Oxygen Species
chemical_list: D004272:DNA, Mitochondrial; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins