Biochemistry · Protein
UCP1 (thermogenin) !
UCP1 is a proton channel in brown fat: it lets the gradient discharge without making ATP, so the energy leaves as heat.
Updated 2026-11-01
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Key facts
- It sits in the inner mitochondrial membrane of brown adipose tissue, plentiful in newborns (between the shoulder blades, neck, around the kidneys).
- Cold activates the sympathetic pathway: noradrenaline → β₃ receptor → lipolysis; the released fatty acids open UCP1.
- Cytosolic purine nucleotides (ATP, ADP, GDP) keep it closed.
- It is the basis of non-shivering thermogenesis in the newborn.
- Also called
- Uncoupling protein 1, Thermogenin
- Genes
- UCP1
- Structure (PDB)
- 8J1N
Regulation
- Activators: long-chain fatty acids released by noradrenaline-driven lipolysis.
- Inhibitors: purine nucleotides; chronic cold raises its expression (and “beige” fat).
Inhibitors and toxins
- ATP, ADP, GTP and GDP (physiological)
Clinical notes
- Preterm babies have little brown fat and lose heat easily; the incubator makes up for what UCP1 cannot produce.
- On FDG-PET, cold-activated brown fat takes up glucose in the neck and supraclavicular area and can mimic lesions.
- 2,4-Dinitrophenol imitates its effect without control (structure 8J1N shows it bound to UCP1).
Pathways
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
What does UCP1 do with the proton gradient?
It discharges it by returning H⁺ to the matrix without passing through ATP synthase: the energy is released as heat.
Which adrenergic receptor activates thermogenesis in brown fat?
β₃; noradrenaline triggers lipolysis and the fatty acids open UCP1.
Which molecules keep UCP1 closed?
Cytosolic purine nucleotides such as ATP and GDP.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: UCP1: Mitochondrial brown fat uncoupling protein 1 (human) (UniProt, 2026); 8J1N: Structure of human UCP1 in the DNP-bound state (RCSB Protein Data Bank, 2026); Mitochondrial Uncoupling (Reactome, 2026).
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Representative model, for educational purposes only.