Hello Haitham,

closed cristae are considered to inhibit apoptotic signalling. Here are links to two publications that explore the mechanistic links between the mitochondrial fusion/cristae remodelling factor OPA1 and apoptosis resistance:

http://www.ncbi.nlm.nih.gov/pubmed/16839885

http://www.ncbi.nlm.nih.gov/pubmed/16839884

Furthermore, this publication shows that Mitofilin controls cytochrome c release during apoptosis by remodelling mitochondrial cristae:

http://www.ncbi.nlm.nih.gov/pubmed/23058921

With best regards,

Christian

Thanks Christian for the links. The 3rd paper is very interesting, but it is actually against our theory. They knocked down Mitofilin, which should result in closed cristae without junctions, but this made the cells more susceptible to apoptotic stimuli. So, closed cristae were not very helpful to resist apoptosis in their model. However, I think their data can also be interpreted as a result of the loss Mitofilin rather than a result of closed cristae, which will make more sense. Do you know of any other publications along the same line?

It is certainly possible that the absence of mitofilin in itself might render the cells more susceptible to apoptosis. I found an interesting study in which the authors studied cristae remodeling in cells treated with the anti-apoptotic protein Bcl-xL:

http://www.ncbi.nlm.nih.gov/pubmed/23288995.

The authors hypothesize that 'the mechanisms of Bcl-xL-mediated remodeling might occur via interaction with formation of CJ protein 1 (Fcj1)' (Fcj1=mitofilin). So maybe Bcl-xL cannot function in anti-apoptotic signaling when mitofilin is missing? I did not find other references to the question how mtofilin might be involved in apoptosis regulation. But it is certainly an intriguing question.

Regrads,

Christian