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Published on: May 3, 2021
Mechanism of uncoupling protein action
K D Garlid1, M Jaburek, P Jezek
1Department of Biochemistry and Molecular Biology, Oregon Graduate Institute of Science & Technology, 20000 N.W. Walker Road, Beaverton, OR 97006-8921, USA. garlid@bmb.ogi.edu
Biochemical Society Transactions
|November 16, 2001
Summary
Uncoupling proteins (UCPs) transport fatty acids (FAs) by their anionic head groups. Proton transport occurs across the membrane bilayer, not through UCPs, confirming Garlid's model.
Area of Science:
- Biochemistry
- Molecular Biology
- Membrane Transport
Background:
- Uncoupling proteins (UCPs) mediate proton transport across mitochondrial membranes, crucial for energy regulation.
- Two models exist for UCP mechanism: Klingenberg's (proton conduction) and Garlid's (anion/fatty acid conduction).
- Fatty acids (FAs) are essential for UCP uncoupling, but their exact transport role is debated.
Purpose of the Study:
- To elucidate the ion transport mechanism of uncoupling proteins (UCPs).
- To differentiate between Klingenberg's and Garlid's models of UCP function.
- To confirm whether UCPs transport protons directly or facilitate fatty acid transport.
Main Methods:
- Utilized FA analogues (long-chain alkylsulphonates) to probe UCP transport.
- Employed ion-pair transport with propranolol and undecanesulphonate to enable proton delivery by sulphonates.
- Assessed GDP-sensitive uncoupling activity in the presence of these compounds.
Main Results:
- Long-chain alkylsulphonates were translocated by UCPs but did not induce uncoupling alone.
- Ion-pair transport of undecanesulphonate with propranolol successfully induced GDP-sensitive uncoupling.
- This demonstrates that the sulphonate head group, analogous to the FA head group, is transported by UCP.
Conclusions:
- The results support Garlid's model, indicating UCPs transport the anionic head group of fatty acids.
- Proton transport, essential for uncoupling, occurs via the membrane bilayer, not directly through the UCP.
- This clarifies the fundamental mechanism of UCP-mediated energy dissipation.
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