RGD Reference Report - Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial alteration. - Rat Genome Database

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Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial alteration.

Authors: Debure, L  Vayssiere, JL  Rincheval, V  Loison, F  Le Drean, Y  Michel, D 
Citation: Debure L, etal., J Cell Sci. 2003 Aug 1;116(Pt 15):3109-21. Epub 2003 Jun 10.
RGD ID: 1582417
Pubmed: PMID:12799419   (View Abstract at PubMed)
DOI: DOI:10.1242/jcs.00619   (Journal Full-text)

Clusterin is a puzzling protein upregulated in many diseased tissues, presented as either a survival or a death protein. The role of clusterin might depend on the final maturation and localization of the protein, which can be secreted or reside inside cells, either after in situ synthesis or uptake of extracellular clusterin. We studied the biological effects of intracellular clusterin and observed that clusterin forms containing the alpha-chain region strongly accumulated in an ubiquitinated form in juxtanuclear aggregates meeting the main criterions of aggresomes and leading to profound alterations of the mitochondrial network. The viability of cells transfected by intracellular forms of clusterin was improved by overexpression of Bcl-2, and caspase inhibition was capable of rescuing cells expressing clusterin, which presented an altered mitochondrial permeability. We propose that, although it might be an inherently pro-survival and anti-apoptotic protein expressed by cells under stress in an attempt to protect themselves, clusterin can become highly cytotoxic when accumulated in the intracellular compartment. This activity might reconcile the opposite purported influences of clusterin on cell survival and explain how clusterin can be causally involved in neurodegeneration.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CluRataggresome  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Clu  (clusterin)


Additional Information