As we are heading from molecular to cell biology I am starting to collect topics that may be of your interest. I just saw this today, published online in Nature (note: NU Library has the paper subscription, so for online first articles you need to wait until it comes out as a print reference, and then they are available). Seems pretty interesting, and is one more addition to the autophagy issue (cells degrade their components for a variety of reasons, among them pure recycling of defective stuff or starvation), which seems to be extremely important for cellular health. Not to mention the mitochondria issue- there seems to be some delicate interplay between mitochondria’s ability to generate ATP and the cell’s needs and abilities to use it. For now, copying the abstract and one picture.

Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure

Takafumi Oka et al

Nature (2012) doi:10.1038/nature10992

Published online 25 April 2012

picture showing Effect of heart overload in normal and DNAse-knockout mice

Effect of heart overload in normal and DNAse-knockout mice- observe the change of size of the heart!

Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure1. However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined. Mitochondria are evolutionary endosymbionts derived from bacteria and contain DNA similar to bacterial DNA234. Mitochondria damaged by external haemodynamic stress are degraded by the autophagy/lysosome system in cardiomyocytes5. Here we show that mitochondrial DNA that escapes from autophagy cell-autonomously leads to Toll-like receptor (TLR) 9-mediated inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy. Cardiac-specific deletion of lysosomal deoxyribonuclease (DNase) II showed no cardiac phenotypes under baseline conditions, but increased mortality and caused severe myocarditis and dilated cardiomyopathy 10 days after treatment with pressure overload. Early in the pathogenesis, DNase II-deficient hearts showed infiltration of inflammatory cells and increased messenger RNA expression of inflammatory cytokines, with accumulation of mitochondrial DNA deposits in autolysosomes in the myocardium. Administration of inhibitory oligodeoxynucleotides against TLR9, which is known to be activated by bacterial DNA6, or ablation of Tlr9 attenuated the development of cardiomyopathy in DNase II-deficient mice. Furthermore, Tlr9 ablation improved pressure overload-induced cardiac dysfunction and inflammation even in mice with wild-type Dnase2a alleles. These data provide new perspectives on the mechanism of genesis of chronic inflammation in failing hearts.