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Bettina Teng, Rebecca S McGreal, Daniel Chauss, Lisa A Brennan, Marc Kantorow; Chaperone-independent mitochondrial translocation, oxidative stress protection and prevention of apoptosis by αB-crystallin. Invest. Ophthalmol. Vis. Sci. 2014;55(13):729.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously demonstrated that αB-crystallin protects lens epithelial cell and retinal pigmented epithelial cell (RPE) mitochondrial function through its ability to directly protect cytochrome c against oxidative inactivation and to preserve the ability of methionine sulfoxide reductase A (MsrA) to repair cytochrome c through reduction of met 80 sulfoxide. We hypothesized that αB-crystallin might protect mitochondria through its chaperone function, here we evaluated the relationship between αB-crystallin chaperone function, mitochondrial membrane potential, cytochrome c release and apoptosis in multiple ocular cell types including lens and RPE cells.
Three forms of αB-crystallin exhibiting different chaperone activity levels including wild type, R120G (decreased chaperone activity) and M68A (increased chaperone activity) were evaluated for their abilities to translocate to the mitochondria, maintain mitochondrial membrane potential, prevent cytochrome c release and maintain viability of ARPE19 cells, SRA04/01 human lens epithelial cells and primary chicken lens epithelial cells.
As expected R120G αB-crystallin exhibited decreased chaperone activity relative to wild type αB-crystallin while M68A exhibited increased chaperone activity relative to wild type αB-crystallin. αB-crystallin protected both lens and RPE cells against oxidative stress damage. Interestingly these forms of αB-crystallin exhibited comparable levels of mitochondrial protection against oxidative stress in RPE cells.
These results confirm that αB-crystallin plays an important role in protecting the mitochondria of multiple cells against oxidative stress damage and therefore plays an important role in the maintenance and protection of multiple ocular cell-types against oxidative stress damage. Surprisingly, the protection of the mitochondria by αB-crystallin appears to be independent of its chaperone activity suggesting dual cellular functions for this important ocular chaperone.
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