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Typical mitochondrial uncouplers are lipophilic weak acids that increase proton transport into the mitochondrial matrix through an ATP synthase-independent pathway, thereby uncoupling nutrient oxidation from ATP production. These chemicals are used to determine rate of cellular respiration and have antioxidant effects that protect from ischemia-reperfusion injury. Most proton transporter uncouplers, however, exhibit off-target activity that can lead to undesired effects, including plasma membrane depolarization, mitochondrial inhibition, and cytotoxicity. BAM15 is a mitochondrial protonophore uncoupler that does not depolarize the plasma membrane and protects mice from acute renal ischemic-reperfusion injury.1 In comparison to FCCP (Item No. 15218), 1-10 µM BAM15 was shown to increase oxygen flux with equal potency as the classic uncoupler, while displaying a higher maximum rate of mitochondrial respiration and less cytotoxicity.1
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1. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol. Metab. 3(2), 114-123 (2013).