Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria.

Article Details

Citation

Cereghetti GM, Stangherlin A, Martins de Brito O, Chang CR, Blackstone C, Bernardi P, Scorrano L

Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria.

Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15803-8. doi: 10.1073/pnas.0808249105. Epub 2008 Oct 6.

PubMed ID
18838687 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoformQ08209Details