We previously showed that mice lacking VHL in the heart succumb to heart failure in ≈10 weeks and display dysregulated metabolism, mitochondrial abnormalities, and increased autophagy.1 Previous studies showed that HIF promotes mitochondrial and peroxisomal autophagy, at least in some settings, presumably to maintain O2 homeostasis under hypoxia.9 Mitochondria and peroxisomes play essential roles in redox, lipid, and energy metabolism.12 Whether the loss of these 2 organelles causes, rather than merely correlates with, heart failure in the setting of chronic ischemia has not been determined. Here, VHL is linked to heart failure.