Endogenous Drp1 Mediates Mitochondrial Autophagy and Protects the Heart Against Energy Stress

 http://circres.ahajournals.org/content/early/2014/10/20/CIRCRESAHA.116.303356.long

In this paper they investigate the role of Drp1 in mediating mitochondrial autophagy and stress resistance in cardiomyocytes.

Cells with down-regulated Drp1 show increases in the amount of cleaved caspase 3 (which activates the caspase and this can result in apoptosis) suggesting that Drp1 plays a role in protection against apoptosis. Also, autophagic flux was reduced upon Drp1 downregulation. Results suggest that Drp1 is required to stimulate mitochondrial degradation through autophagy.

There were significantly more mitochondria in cells with Drp1 downregulation, suggesting that the reduction in autophagy leads to an accumulation of mitochondria. Expression of PGC-1a (which causes mitochondrial biogenesis) was the same as in control cells. ATP production was lower in Drp1 downregulated cells, membrane potential was lower and mPTP opening was likely to be accelerated (increased mPTP opening could have been the reason why apoptosis was seen more). Maximum respiratory rate was lower, but the amount of proton leak was not significantly different.