In mouse and human prostate cancer models, Chen et al. found that mitochondrial PDC provides cytosolic citrate for lipid synthesis, whereas nuclear PDC is critical for the acetylation of H3K9 and the expression of sterol regulatory element-binding transcription factor (SREBF) target genes, such as ACLY and squalene epoxidase (SQLE). Here, PDC is linked to Familial prostate cancer.