Mitochondrial retention of Opa1 is required for mouse embryogenesis.

Mammalian Genome : Official Journal of the International Mammalian Genome Society
Billie A MooreTamara Caspary

Abstract

Mitochondria are dynamic cellular organelles that balance fission and fusion to regulate organelle morphology, distribution, and activity, and Opa1 is one of three GTPases known to regulate mitochondrial fusion. In humans, loss of a single Opa1 allele causes dominant optic atrophy, a degenerative condition that leads to loss of vision. Here we demonstrate that the lilR3 mutant mouse phenotype is due to a point mutation in the Opa1 gene resulting in mislocalized Opa1 protein from the mitochondria to the cytosol. Importantly, the mutation is in the middle domain of the Opa1 protein, for which no function had been described. Lack of mitochondrial retention of Opa1 is sufficient to cause the cellular Opa1 loss-of-function phenotype as the mitochondria are fragmented, indicating an inability to fuse. Despite the normally ubiquitous expression of Opa1 and the essential nature of mitochondria, embryos with aberrant Opa1 survived through midgestation and died at E11.5. These mutants displayed growth retardation, exencephaly, and abnormal patterning along the anterior-posterior axis, although the A-P axis itself was intact. The complex relationship between mitochondrial dynamics and cell death is emphasized by apoptosis in specific cell...Continue Reading

References

Sep 6, 1991·Cell·G ChalepakisP Gruss
May 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·H PetersJ Niessing
Feb 1, 1996·Acta Ophthalmologica Scandinavica·B KjerT Rosenberg
Jan 1, 1996·Journal of Inherited Metabolic Disease·J Marin-GarciaA Perez-Atayde
Sep 1, 1995·Journal of Cardiac Failure·J Marin-GarciaR Ananthakrishnan
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·A KasarskisK V Anderson
Oct 24, 1998·The Journal of Cell Biology·G J HermannJ M Shaw
Sep 24, 1999·Methods : a Companion to Methods in Enzymology·R M ZuckerJ M Rogers
Nov 13, 1999·Nature Cell Biology·W BleazardJ M Shaw
May 10, 2000·Nature Medicine·G Kroemer, J C Reed
Oct 19, 2000·The Journal of Cell Biology·P FekkesM P Yaffe
Nov 18, 2000·The Journal of Physiology·R RizzutoT Pozzan
Nov 18, 2000·The Journal of Physiology·M R Duchen
Dec 21, 2000·Cardiovascular Research·J Marin-GarciaG W Moe
Aug 22, 2001·Molecular Biology of the Cell·E SmirnovaA M van der Bliek
Jan 26, 2002·Human Genetics·C DelettreC P Hamel
Jun 5, 2003·The Journal of Biological Chemistry·Dominic I JamesJean-Claude Martinou
Feb 19, 2004·The Journal of Biological Chemistry·Lorena GriparicAlexander M van der Bliek
Feb 21, 2004·Current Topics in Developmental Biology·Hsiuchen Chen, David C Chan
Sep 10, 2004·Molecular Biology of the Cell·Yang-ja LeeRichard J Youle
Oct 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sara CipolatLuca Scorrano
Mar 10, 2005·Proceedings of the National Academy of Sciences of the United States of America·María J García-GarcíaKathryn V Anderson
May 19, 2005·The Journal of Biological Chemistry·Hsiuchen ChenDavid C Chan
Oct 22, 2005·Annals of Neurology·Patrizia Amati-BonneauPascal Reynier
Jan 18, 2006·Mechanisms of Development·Ramin Mollaaghababa HakamiWilliam J Pavan
Sep 28, 2006·The Journal of Biological Chemistry·Stéphane Duvezin-CaubetAndreas S Reichert
Dec 15, 2006·Journal of Cellular Physiology·Aurélien OlichonPascale Belenguer
Feb 23, 2007·Brain : a Journal of Neurology·Marcel V AlaviBernd Wissinger

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Citations

Apr 27, 2011·International Journal of Cancer. Journal International Du Cancer·Xiao-Qun YeGui-Sheng Qian
Aug 21, 2012·Biochimica Et Biophysica Acta·Pascale Belenguer, Luca Pellegrini
Nov 30, 2010·Progress in Retinal and Eye Research·Patrick Yu-Wai-ManPatrick F Chinnery
Dec 10, 2014·Nature Reviews. Neurology·Florence BurtéPatrick Yu-Wai-Man

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