Nucleotide synthesis—the production of the basic components of DNA and RNA—is essential for cell growth and division. In most animal cells, this process depends closely on properly functioning mitochondria, the organelles responsible for respiration and energy production. When mitochondrial respiration fails—a common feature of mitochondrial diseases and several forms of cancer—cells lose the ability to proliferate normally. A new study published in Nature Metabolism now shows that this dependence is not irreversible.