HK2 and melanoma: Several potential mechanisms resulting in BRAFi-induced mitochondrial reprogramming could be proposed: (i) mobilization of mitochondrial biogenesis through reactivation of the MITF-PGC-1α pathway [45, 47], which appears to also be controlled by mTORC1/2 [35]; (ii) inhibition of the HIF-1α/PDK pathway [5, 50], the major gatekeeper of mitochondrial activity in melanoma [90]; and (iii) decreased HK2 expression [50], which usually contributes to inhibiting mitochondrial OXPHOS [91].