Mitochondria and Shock —

These are such ingenious and clever two papers

Serious physical injury, or trauma, is a major cause of morbidity and mortality worldwide, Patients who survive the initial trauma, despite medical and surgical care, often remain critically ill. One cause of this extension of danger is the systemic inflammatory response syndrome with shock and compromised function of several organs. The clinical symptoms of post-traumatic syndromes, fever, increased heart rate and low blood pres¬sure (shock) are similar to the signs and symptoms of the systemic inflammatory response to severe infection, i.e. sepsis. The molecu¬lar mechanism of these severe problems has been poorly understood.

In Nature 4th March 2010 Zhang et al. identify one of the pathways that triggers trauma-associated syndromes and links it to pathways implicated in sepsis-associated syndromes.

It was previously proposed that traumatic stress syndrome was due to bacterial escaping from the bowel and infecting the patient. Zhang et al suggest that mitochondria are the link. Mitochondria are believed to be organelles that originated from bacteria that parasitized eukaryotic cells and retain many similarities with bacteria. So during trauma these mitochondria pour out of the damaged tissues and cause a form of sepsis.

Calfee and Matthay 2010 Culprits with evolutionary ties Nature vol 464 pp 41-42

Zhang 2010 Circulating mitochondrial DAMPs cause inflammatory responses to injury Nature vol 464 pp 104-107

Mitochondrial Bar Codes —

Mitochondria, the cell’s energy producers, are descended from free-living bacteria that took up residence within other cells some 2 billion years ago. They have a modest genetic size being only 37 genes in vertebrates, compared with more than 20,000in a nucleus.

Yet within this little genome, researchers have identified a 64S-nucleotide stretch as the ultimate identifier of species, dubbed the DNA bar code. The sequence can distinguish between closely related species such as humans and chimps and even classify new species from identical-looking ones, such as the blue-flasher butterfly (Astraptes fulgerator), which has since been divided into ten separate species, verified by the habitats, lifestyles and diets of their caterpillars. ,

The DNA bar code has been both praised and attacked for its simplicity.

Lane 2009 On the origins of bar codes Nature vol 462 pp272-3

Mitochondrial Genes —

Mitochondria have important roles in cellular processes, for example, production of cellular energy in the form of ATP and pro¬grammed cell death (apoptosis). Each mitochondrion contains between two and ten copies of mtDNA. Cells have numerous mitochondria, a cell may harbour several thousand mtDNA copies. Mutations in mtDNA occur at a tenfold or higher rate than in nuclear DNA, possibly due to a high concentration of free oxygen radicals, lack of histones and limited mtDNA repair mechan¬isms.

Diseases caused by mtDNA mutations are numerous, over 150 mutations (including 100 deletions and approximately 50 point mutations) have been identified that are associated with serious human disorders, including myopathies, neu¬rodegenerative diseases, diabetes, cancer and infertility. mtDNA mutations are increasingly implicated in Alzheimer’s, Parkinson’s and Huntington’s diseases.

Typically, a cell contains only one type of mtDNA (homoplasmy). If an individual cell contains two or more types of mtDNA-that is, as a mixture of normal and mutant mtDNA, the phenomenon is known as heteroplasmy. Heteroplasmy allows lethal mutations to persist and most importantly to pass to the next generation. MtDNA is maternally inherited through the egg’s cytoplasm, whereas sperm mitochondria constitute a minor fraction of the zygote’s cohort and are rapidly eliminated after fertilization.

Possibly 1 in 3,500-6000 people has either mtDNA disease or is at risk for development of mtDNA-based disorders, most of which are incurable.

Tachibana et al (2009) Mitochondrial gene replacement in primate offspring and embryonic stem cells. .Nature vol 461 pp 367-372