The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 10 Jun 2003
doi: 10.1242/jcs.00619
Research Article
Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial alteration
Laure Debure*,
Jean-luc Vayssière,
Vincent Rincheval,
Fabien Loison,
Yves Le Dréan,
and
Denis Michel
* Author for correspondence (e-mail: laure.debure{at}univ-rennes1.fr)
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
-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.
This article has been cited by other articles:

|
 |

|
 |
 
V. Devauchelle, A. Essabbani, G. De Pinieux, S. Germain, L. Tourneur, S. Mistou, F. Margottin-Goguet, P. Anract, H. Migaud, D. Le Nen, et al.
Characterization and Functional Consequences of Underexpression of Clusterin in Rheumatoid Arthritis
J. Immunol.,
November 1, 2006;
177(9):
6471 - 6479.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Scaltriti, A. Santamaria, R. Paciucci, and S. Bettuzzi
Intracellular Clusterin Induces G2-M Phase Arrest and Cell Death in PC-3 Prostate Cancer Cells1
Cancer Res.,
September 1, 2004;
64(17):
6174 - 6182.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. P. Trougakos, A. So, B. Jansen, M. E. Gleave, and E. S. Gonos
Silencing Expression of the Clusterin/Apolipoprotein J Gene in Human Cancer Cells Using Small Interfering RNA Induces Spontaneous Apoptosis, Reduced Growth Ability, and Cell Sensitization to Genotoxic and Oxidative Stress
Cancer Res.,
March 1, 2004;
64(5):
1834 - 1842.
[Abstract]
[Full Text]
[PDF]
|
 |
|
© The Company of Biologists Ltd 2003