Membrane Lipid Reshaping Underlies Oxidative Stress Sensing by the Mitochondrial Proteins UCP1 and ANT1

Oxidative stress and ROS are important players in the pathogenesis of numerous diseases. In addition to directly altering proteins, ROS also affects lipids with negative intrinsic curvature such as phosphatidylethanolamine (PE), producing PE adducts and lysolipids. The formation of PE adducts potent...

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Bibliographic Details
Published in:Antioxidants 2022-11, Vol.11 (12), p.2314
Main Authors: Jovanović, Olga, Chekashkina, Ksenia, Škulj, Sanja, Žuna, Kristina, Vazdar, Mario, Bashkirov, Pavel V, Pohl, Elena E
Format: Article
Language:English
Subjects:
Adducts
Adenosine
bending moduli
lateral pressure profile
Lipid bilayers
lipid shape
Lipids
lipid–protein interaction
Mechanical properties
Membrane lipids
Membranes
Mitochondria
mitochondrial membrane protein
Observations
Oxidative stress
Phosphatidylethanolamine
Physiological aspects
Proteins
reactive aldehydes
Translocase
Uncoupling protein 1
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Summary:Oxidative stress and ROS are important players in the pathogenesis of numerous diseases. In addition to directly altering proteins, ROS also affects lipids with negative intrinsic curvature such as phosphatidylethanolamine (PE), producing PE adducts and lysolipids. The formation of PE adducts potentiates the protonophoric activity of mitochondrial uncoupling proteins, but the molecular mechanism remains unclear. Here, we linked the ROS-mediated change in lipid shape to the mechanical properties of the membrane and the function of uncoupling protein 1 (UCP1) and adenine nucleotide translocase 1 (ANT1). We show that the increase in the protonophoric activity of both proteins occurs due to the decrease in bending modulus in lipid bilayers in the presence of lysophosphatidylcholines (OPC and MPC) and PE adducts. Moreover, MD simulations showed that modified PEs and lysolipids change the lateral pressure profile of the membrane in the same direction and by the similar amplitude, indicating that modified PEs act as lipids with positive intrinsic curvature. Both results indicate that oxidative stress decreases stored curvature elastic stress (SCES) in the lipid bilayer membrane. We demonstrated that UCP1 and ANT1 sense SCES and proposed a novel regulatory mechanism for the function of these proteins. The new findings should draw the attention of the scientific community to this important and unexplored area of redox biochemistry.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox11122314