Chaperone-independent mitochondrial translocation and protection by alpha B-crystallin in RPE cells

alpha B-crystallin is a small heat shock protein that exhibits chaperone activity and can protect multiple cell types against oxidative stress damage. Altered levels and specific mutations of alpha B-crystallin are associated with multiple degenerative diseases. We previously found that alpha B-crystallin translocates to lens and retinal cell mitochondria upon oxidative stress exposure where it provides protection against oxidative stress damage. To date, the role of the chaperone function of alpha B-crystallin in mitochondrial translocation and protection has not been established. Here, we sought to determine the relationship between the chaperone activity of alpha B-crystallin and its ability to translocate to and protect retinal cell mitochondria against oxidative stress damage. Our data provide evidence that three forms of alpha B-crystallin exhibiting different chaperone activity levels including wild-type, R120G (decreased chaperone activity) and M68A (increased chaperone activity) provide comparable levels of mitochondrial translocation and protection to retinal cells exposed to oxidative stress. The results provide evidence that mitochondrial translocation and protection by alpha B-crystallin is independent of its chaperone activity and that other functions of alpha B-crystallin may also be independent of its chaperone activity. (C) 2013 Elsevier Ltd. All rights reserved.