Optineurin Increases Cell Survival and Translocates to the Nucleus in a Rab8-dependent Manner upon an Apoptotic Stimulus*

In glaucoma the retinal ganglion cells of the retina die through the induction of apoptosis leading to excavation of the optic nerve and blindness. Mutations in the optineurin (optic neuropathy inducing) protein were found associated with an adult form of glaucoma. To date, the role of optineurin in the neurodegeneration process that occurs during glaucoma is still unknown. We now report that in response to an apoptotic stimulus, optineurin changes subcellular localization and translocates from the Golgi to the nucleus. This translocation is dependent on the GTPase activity of Rab8, an interactor of optineurin. Furthermore, we demonstrate that the overexpression of optineurin protects cells from H2O2-induced cell death and blocks cytochrome c release from the mitochondria. A mutated form of optineurin, E50K, identified in normal tension glaucoma patients loses its ability to translocate to the nucleus and when overexpressed compromises the mitochondrial membrane integrity resulting in cells that are less fit to survive under stress conditions. The correlation between optineurin function and cell survival will be key to begin to understand retinal ganglion cell biology and signaling and to design general “survival” strategies to treat a disease of such a complex etiology as glaucoma.

• Publication year

  2006

• Venue

  Journal of Biological Chemistry

• Publication date

  2006-06-09

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M601467200PMID 16569640
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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