DEPP autophagy regulator 1 (DEPP1)

DEPP autophagy regulator 1 (DEPP1) is a stress-inducible protein involved in the modulation of autophagy, particularly under conditions of fasting, metabolic stress, and hypoxia. It contains a SNARE coiled-coil homology domain and a peroxisomal targeting signal, allowing localization to mitochondria and peroxisomes. DEPP1 is directly regulated by HIF and FOXO transcription factors, and is necessary and sufficient for hypoxia-induced autophagy, mitochondrial and peroxisomal turnover, and triglyceride deposition, especially in cardiomyocytes. Loss of DEPP1 is protective in models of heart disease and insulin resistance, and its overexpression correlates with pathologies such as cancer and osteoarthritis. DEPP1’s molecular function is distinct from core autophagy machinery; it acts independently of mTOR inhibition and links metabolic stress signaling to organelle-specific autophagy.

Other names

C10orf10DEPPFIGFsegdecidual protein induced by progesteronefasting-induced gene proteinfat-specific expressed genefasting inducedfat-specific expressedprotein DEPPDEPP1 autophagy regulatorfasting-induced protein

Drugs activating HIF (such as FG-4592) indirectly increase DEPP1 expression, promoting autophagy and lipid accumulation in cardiomyocytes. DEPP1 acts as a downstream effector of FOXO-mediated and HIF-mediated autophagy.