UNIGE document Scientific Article
previous document  unige:2380  next document
add to browser collection

Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria

Cereghetti, G M.
Stangherlin, A.
Martins de Brito, Olga
Chang, C R.
Blackstone, C.
Bernardi, P.
Published in Proceedings of the National Academy of Sciences. 2008, vol. 105, no. 41, p. 15803-8
Abstract Changes in mitochondrial morphology that occur during cell cycle, differentiation, and death are tightly regulated by the balance between fusion and fission processes. Excessive fragmentation can be caused by inhibition of the fusion machinery and is a common consequence of dysfunction of the organelle. Here, we show a role for calcineurin-dependent translocation of the profission dynamin related protein 1 (Drp1) to mitochondria in dysfunction-induced fragmentation. When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. Thus, fragmentation of depolarized mitochondria depends on a loop involving sustained Ca(2+) rise, activation of calcineurin, and dephosphorylation of Drp1 and its translocation to the organelle.
Keywords Calcineurin/metabolism/physiologyCalciumGTP Phosphohydrolases/metabolismHela CellsHumansMembrane Potential, MitochondrialMicrotubule-Associated Proteins/metabolismMitochondria/metabolismMitochondrial Proteins/metabolismMutagenesis, Site-DirectedPhosphorylationProtein TransportSerine
PMID: 18838687
Full text
Research group Les mitochondries dans la vie cellulaire (850)
(ISO format)
CEREGHETTI, G M. et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. In: Proceedings of the National Academy of Sciences, 2008, vol. 105, n° 41, p. 15803-8. doi: 10.1073/pnas.0808249105 https://archive-ouverte.unige.ch/unige:2380

445 hits



Deposited on : 2009-08-10

Export document
Format :
Citation style :