“Cells live in a watery world, even when the organisms of which they are part do not,” wrote Christian de Duve in his 1984 book, A guided tour of the living cell. Most human cells, for instance, are immersed in fluids that render their vast inner space jelly-like. Floating within this cytoplasmic soup are mitochondria, ribosomes, vacuoles, and many other so-called organelles—tiny instruments that carry out a cell’s basic functions.
Inspired by the films of Jacques Cousteau, de Duve wanted his readers to embark on the journey with the mindset of a “cytonaut” ready to explore “a strange world, fascinating, mysterious, but very far removed from our everyday experience.” The late cell biologist was himself a pioneer who, together with Albert Claude and George E. Palade, spent the 1940s and 50s detailing the first functional map of the cell—work for which the three Rockefeller scientists later shared a Nobel Prize.
A must-see along the tour is the lysosome, a bubble-shaped organelle that de Duve was the first to set eyes on in 1955, and whose acidic interior was subsequently found to serve various purposes, like breaking down cellular debris. Yet it wasn’t until early this year that scientists discovered that our cells need this sour little sac to process iron, an essential nutrient, into a form they can metabolize in order to survive. This may in fact be the most important of the lysosome’s functions.
Graduate student Ross Weber made the discovery in a lab not far from the one de Duve once inhabited. There, he manipulated cells to make their lysosomes less acidic, in an experiment that had to be controlled with minute precision. For reasons that have long been unknown, cells will stop dividing and die if the pH within lysosomes raises above a certain threshold.
Today Weber and other members of the lab, led by Kivanç Birsoy, have a possible explanation for this phenomenon: Their experiments showed that cells with more-alkaline lysosomes suffer iron depletion—and as a result, they lose their ability to produce essential molecules like DNA. “Lysosomes participate in a lot of different cell functions like signaling, metabolism and recycling,” says Birsoy, who is Rockefeller’s Chapman Perelman Assistant Professor, “but processing iron seems to be the only thing cells really cannot do without them.”
He hopes the new research, published in Molecular Cell, might lead to the development of novel cancer therapies. Several types of tumors cells are known to be sensitive to elevated lysosome pH, and the new findings suggest it’s the ensuing iron deficiency that brings these tumor cells the fatal blow. This could mean that depleting tumors of iron offers an effective way to kill them, says Birsoy, and is the latest possibility to come out of his lab’s extensive effort to develop new treatments that starve tumors for nutrients they cannot produce on their own.
The team also plans to find out whether the new findings could be relevant to other conditions linked to the loss of lysosome acidity, including a group of rare metabolic disorders and neurodegenerative diseases. “We believe there are a lot of exciting possibilities out there,” Birsoy says.
Moreover, the lysosome isn’t the only organelle whose inner secrets might yield ideas for new medicines. Mitochondria, for example, the cell’s peanut-shaped powerhouses, are the targets of several promising cancer treatments. And who knows what other treasures may await 21st-century cytonauts as they plunge deeper down the cellular sea.
Source: Rockefeller University