M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress - PubMed
7 days ago
- #AMPK signaling
- #Ubiquitination
- #Metabolic stress
- M1-linked ubiquitination by LUBAC regulates AMPK signaling and cellular response to energetic stress.
- LUBAC and OTULIN dynamically regulate the energy-sensing kinase AMPK, crucial for cellular and organismal energy balance.
- HOIP, a catalytic subunit of LUBAC, is essential for full AMPK activation during energetic stress, while OTULIN counteracts this response.
- LUBAC directly ubiquitinates AMPKα and β subunits, marking AMPK as a substrate for M1-linked ubiquitination.
- Loss of LUBAC impairs AMPK activation, reduces bioenergetic adaptability, and increases sensitivity to starvation-induced cell death.
- Drosophila studies show that absence of Lubel (LUBAC orthologue) leads to defective AMPK activation and reduced survival under starvation.
- The findings highlight M1-linked ubiquitination as a novel regulatory mechanism for AMPK activation and metabolic adaptability.