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This week in PLOS Biology

In PLOS Biology this week, you can read about moving lipids around the cell, good and bad autophagyhow skin cancer metastasises, and mending DNA replication forks safely.

 

 Moving Lipids from Organelle to Organelle

Prinz thumbMoving lipids and proteins from the endoplasmic reticulum to the mitochondria (and vice versa) is a vital process, but the mechanism of transfer which occurs when regions of these organelles are in close contact is not known. Sujoy Lahiri, William Prinz and colleagues used a genetic screen in Saccharomyces cerevisiae yeast to identify mutants with defects in lipid exchange. They then reported that a protein complex called EMC present in the endoplasmic reticulum is important for tethering it to mitochondria. They propose that the EMC interacts with the mitochondrial outer membrane complex TOM, placing the two organelles in close apposition and aiding the transfer of lipids. Failure to do this results in cell death, showing that the process is essential for life.

 

Autophagy: Making Sense of a Double-Edged Sword

Autophagy is the mechanism by which cellular material is delivered to lysosomes and degraded. The extensive literature on this process brings us to the conclusion that sometimes it is good and sometimes it is bad. For example, there was a recent attempt to inhibit autophagy in a child with a brain tumour. So if we understood more about how autophagy impacts on health and disease, could we improve treatment and prevention? This is the question asked in a new Essay by Andrew Thorburn. He reviews our knowledge of autophagy and bacterial infection, cancer and cell death. He concludes that mechanistic understanding of biological processes will lead to practical applications, and that the current rapid pace of progress is encouraging.

 

Melanoma Cells: A Fatal Attraction for LPA

Credit: doi:10.1371/journal.pbio.1001966
Credit: doi:10.1371/journal.pbio.1001966

Melanoma is a highly metastatic and aggressive form of cancer. In a fascinating new study, Andrew Muinonen-Martin, Robert Insall and colleagues address what drives melanoma cells to start migrating out from the tumour – a poorly understood process. They focussed on the chemical signals that guide tumour cell migration. In both cell lines and in mice, they showed the importance of the breakdown of a lipid called lysophosphatidic acid (LPA). A gradient is created, with higher concentrations of LPA further away from the tumour, which acts as a chemoattractant, drawing tumour cells out into surrounding skin and blood vessels. These findings could have important implications for new treatment avenues for skin cancer. Read more in this blog post by Ines Alvarez-Garcia.

 

Reining in the Copy-Editors

Maintaining genetic fidelity is of paramount importance to living organisms. During DNA replication, obstacles to the progression of DNA replication forks can trigger repair by patching in the correct DNA sequence, using the second copy of that chromosome as a template – a process known as homologous recombination. However, use of the wrong template can result in genome rearrangements, such as those often observed in cancer and genomic disorders. Violena Pietrobon, Sarah Lambert and colleagues investigated how the delicate balance between insufficient and excessive homologous recombination is maintained, identifying an evolutionarily conserved interplay between CAF-1 (a chromatin assembly factor) and RecQ-type helicases that helps to maintain genome stability in the face of replication stress.

 

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