In a recent study published in Cell Death and Discovery, it has been shown that energy homeostasis and adaptation to metabolic stress in cancer cells are primarily achieved by integrated response exerted by activation of an energy sensor, AMPK.3 The study provides evidence that the AMPK–p38–PGC1-α axis, by increasing mitochondrial biogenesis, supports oxidative metabolism of non-glucose substrates to maintain the cellular ATP pool. Here, PPARGC1A is linked to cancer.