Bioethics Blogs

Creative Minds: Of Arsenic and Misfolded Proteins

John Hanna

Taking out the trash is a must in every household. Inside our cells, it’s also essential because if defective proteins are not properly disposed of, they can accumulate and make a mess of the cell’s inner workings, leading to health problems.

John Hanna, a physician-scientist at Brigham and Women’s Hospital, Boston, is on a quest to study the cell’s trash disposal system in greater detail. In particular, this 2014 NIH Director’s Early Independence awardee wants to learn more about how cells identify proteins that need to be discarded, how such proteins are steered towards the molecular garbage can, and how, when the process breaks down, neurodegenerative conditions, cancers, and other diseases can arise.

That’s a complex challenge, so Hanna will start by zeroing in on one particular component of cellular waste management—the component that clears out proteins damaged by arsenic. Although arsenic is notorious for being the poison of choice in countless true crime shows and mystery novels, this semi-metallic element is found naturally in soil, water, air, and some foods.

Cells can detoxify low levels of arsenic, but can handle only so much before the stuff begins interacting with normal proteins, causing them to destabilize, unfold, and accumulate in toxic aggregates. To help keep this from happening, an important component of the cell’s waste-management system kicks in: a molecule called ubiquitin tags misfolded proteins, marking them for removal. Tagged proteins are then transported to amazing nanomachines called proteasomes, which are barrel-shaped structures located within the cell. There they are routed through an elaborate system of enzymes and other molecules to degrade and recycle their parts.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.