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Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA

James, Dominic I.
Published in PLOS ONE. 2008, vol. 3, no. 9, p. e3257
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.
Keywords Adenosine Triphosphate/metabolismAutophagyCell ProliferationDNA, Mitochondrial/metabolismGTP Phosphohydrolases/metabolismGene Expression RegulationHela CellsHomeostasisHumansMembrane Potential, MitochondrialMicrotubule-Associated Proteins/metabolismMitochondria/metabolism/physiologyMitochondrial Proteins/metabolismModels, BiologicalOxygen ConsumptionRNA InterferenceReactive Oxygen Species
PMID: 18806874
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Research groups Translocation des protéines à travers les membranes (169)
Mitochondries et sécrétion d'insuline (671)
(ISO format)
PARONE, Philippe et al. Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA. In: PLOS ONE, 2008, vol. 3, n° 9, p. e3257. https://archive-ouverte.unige.ch/unige:2437

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Deposited on : 2009-08-13

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