Oncometabolites: Unconventional triggers of oncogenic signalling cascades

•Altered metabolism is an emerging aspect of tumorigenesis.•Damaged mitochondria accumulate metabolites that can activate oncogenic cascades.•Environmental and nutritional cues trigger the accumulation of these metabolites.

Cancer is a complex and heterogeneous disease thought to be caused by multiple genetic lesions. The recent finding that enzymes of the tricarboxylic acid (TCA) cycle are mutated in cancer rekindled the hypothesis that altered metabolism might also have a role in cellular transformation. Attempts to link mitochondrial dysfunction to cancer uncovered the unexpected role of small molecule metabolites, now known as oncometabolites, in tumorigenesis. In this review, we describe how oncometabolites can contribute to tumorigenesis. We propose that lesions of oncogenes and tumour suppressors are only one of the possible routes to tumorigenesis, which include accumulation of oncometabolites triggered by environmental cues.