Article

Journal of Bioenergetics and Biomembranes

, Volume 31, Issue 5, pp 475-491

First online:

UCP1: The Original Uncoupling Protein—and Perhaps the Only One? New Perspectives on UCP1, UCP2, and UCP3 in the Light of the Bioenergetics of the UCP1-Ablated Mice

  • Jan NedergaardAffiliated withThe Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University
  • , Anita MatthiasAffiliated withThe Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University
  • , Valeria GolozoubovaAffiliated withThe Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University
  • , Anders JacobssonAffiliated withThe Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University
  • , Barbara CannonAffiliated withThe Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University

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Abstract

The availability of a UCP1-ablated mouse has enabled critical studies of the function of UCP1,UCP2, and UCP3. Concerning UCP1, its presence in brown-fat mitochondria is associatedwith innate uncoupling, high GDP-binding capacity, and GDP-inhibitable Cl- permeabilityand uncoupling—but the high fatty acid sensitivity found in these mitochondria is observedeven in the absence of UCP1. The absence of UCP1 leads to low cold tolerance but not toobesity. UCP1 ablation also leads to an augmented expression of UCP2 and UCP3 in brownadipose tissue, making this tissue probably the one that boasts the highest expression ofthese UCPs. However, these very high expression levels are not associated with any inherentuncoupling, or with a specific GDP-binding capacity, or with a GDP-sensitive Cl- permeability,or with any effect of GDP on mitochondrial membrane potential, or with an increased basalmetabolism of cells, or with the presence of norepinephrine- or fatty acid-induced thermogenesisin cells, and not with a cold-acclimation recruited, norepinephrine-induced thermogenicresponse in the intact animal. Therefore, it can be discussed whether any uncoupling effect isassociated with UCP2 or UCP3 when they are endogenously expressed and, consequently,whether (loss of) uncoupling (thermogenic) effects of UCP2 or UCP3 can be invoked toexplain metabolic phenomena, such as obesity.

Uncoupling proteins nonshivering thermogenesis brown-fat mitochondria liver mitochondria norepinephrine mitochondrial membrane potential obesity