Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA.
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.
Parone
Philippe A
PA
Department of Cell Biology, University of Geneva, Geneva, Switzerland.
Da Cruz
Sandrine
S
Tondera
Daniel
D
Mattenberger
Yves
Y
James
Dominic I
DI
Maechler
Pierre
P
Barja
François
F
Martinou
Jean-Claude
JC
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
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