Tuesday, 4 February 2014

Mitochondria supply membranes for autophagosome biogenesis during starvation

http://www.ncbi.nlm.nih.gov/pubmed/20478256

During starvation, autophagy is increased so that the cell can degrade its own components to retrieve nutrients. But where do the membranes that form the autophagosomes come from?

In this paper, they show that lipids for forming autophagosomes come from the outer membrane of mitochondria. The forming of autophagosomes is inhibited if cells lack MFN2, a protein necessary for mitochondrial fusion and also for tethering mitochondria to the ER. They think that the ER can resupply lipids to the mitochondrion (to make up for the lipids it lost to form the autophagosomal membrane (AM)).  But doesn't the mitochondrion lose its outer membrane proteins by using part of his membrane to form AMs? Apparently it does not. Most outer membrane proteins of mitochondria are not seen in the AM, which is hypothesized to be the result of a diffusion barrier for proteins. Only proteins associated with the outer leaflet of the outer mitochondrial membrane can traverse the barrier.

Interestingly, lipids from mitochondria only play a role in forming AMs if forming of autophagosomes is induced by starvation. Other mechanisms that induce autophagy (e.g. ER stress and calcium perturbations) do not show mitochondrial outer membrane components colocalized with EM.

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