Thursday, March 16, 2017

That poor old C57Bl/6 mouse

There is a is a link within the Guarás et al CoQ paper I put up in the last post (which I'll probably go back to in some detail in future posts). It's to a paper by Lapuente-Brun et al:

Supercomplex Assembly Determines Electron Flux in the Mitochondrial Electron Transport Chain

Here is my doodle, butchered from elsewhere, of the  Supercomplex (SC), also known as the Respirasome:

The things to note are the assembly of complexes I, III and IV in to one unit and that there are enclosed molecules of both CoQ and Cytochrome C within the SC. These electron transporters are isolated from their respective general membrane pools so as to ensure maximal efficiency of electron transfer within the integrated SC.

The SC doesn't just happen. It's glued together by specific assembly proteins. In particular C III and C IV are joined by a protein called Cox7A2l (to be renamed supercomplex assembly factor I, SCAFI).

Unless you are a C57Bl/6 mouse.

If you are a C57/Bl/6 mouse your SCAFI  is 4 amino acids too short. It doesn't work.

The whole, excellent, paper by Lapuente-Brun et al is really about supercomplex formation and preferential assembly of the basic complexes. But because it uses the broken C57Bl/6 as an example of defective respiration it does bring home how irrelevant this particular mouse might be to more humans with a more normal metabolism.

Quite how this defect of SC assembly might make that the C57Bl/6 mouse in to the strange metabolic item which it is is not clear.

But, at the core of normal respiratory supercomplex formation, the Bl/6 mouse broken. That's an awful lot of mouse research which is broken. You could almost feel sorry for obesity researchers. But not quite.

Just sayin'.


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