Activating mutations in BRAF are the most common genetic alterations in 
melanoma. Inhibition of BRAF by small molecules leads to cell-cycle arrest and 
apoptosis. We show here that BRAF inhibition also induces an oxidative 
phosphorylation gene program, mitochondrial biogenesis, and the increased 
expression of the mitochondrial master regulator, PGC1α. We further show that a 
target of BRAF, the melanocyte lineage factor MITF, directly regulates the 
expression of PGC1α. Melanomas with activation of the BRAF/MAPK pathway have 
suppressed levels of MITF and PGC1α and decreased oxidative metabolism. 
Conversely, treatment of BRAF-mutated melanomas with BRAF inhibitors renders 
them addicted to oxidative phosphorylation. Our data thus identify an adaptive 
metabolic program that limits the efficacy of BRAF inhibitors.