Give it or take it: the flux of one-carbon in cancer cells

The sequence of the human genome together with sequence similarity analyses has advanced the discovery of missing steps in the mitochondrial one-carbon metabolism pathway. That together with the revived interest in cancer metabolism has brought the research on one-carbon metabolism back under the spotlight. Here, we present a brief review of recent advances in the field of one-carbon metabolism, with a bias towards its relevance to cell growth and proliferation in human cancers. We will address the requirements of one-carbon metabolism for biosynthesis and the major sources to satisfy that demand. We will also discuss some recent discoveries indicating a role of one-carbon metabolism beyond biosynthesis. We conclude with a concise enumeration of some fundamental questions that remain unanswered.