Experiments using functional VHL-deficient renal cell carcinoma cell lines revealed that HIF-1 can reduce mitochondrial biogenesis by inducing the expression of MAX interactor 1 (MXI-1), which represses c-Myc transcriptional activity, and promoting MXI-1-independent but proteasome-dependent degradation of c-Myc. Here, MYC is linked to hereditary clear cell renal cell carcinoma.