Gene

DNAJA3

Mitochondrial carrier

Bacterial outer membrane

mitochondrial fusion

Adipose tissue

Apoptosis

Autophagy

Mitochondrial DNA

Mitochondrial ROS

Uncoupling protein

Brown adipose tissue

Mitochondrion

Uncoupling Agents

Reactive oxygen species

Escherichia coli

Biochemistry

Thermogenin

Biology

Cell biology

Cells

Mitochondrial uncoupling can be defined as a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis. Although this process was originally considered a mitochondrial dysfunction, the identification of UCP-1 as an endogenous physiological uncoupling protein suggests that the process could be involved in many other biological processes. In this review, we first compare the mitochondrial uncoupling agents available in term of mechanistic and non-specific effects. Proteins regulating mitochondrial uncoupling, as well as chemical compounds with uncoupling properties are discussed. Second, we summarize the most recent findings linking mitochondrial uncoupling and other cellular or biological processes, such as bulk and specific autophagy, reactive oxygen species production, protein secretion, cell death, physical exercise, metabolic adaptations in adipose tissue, and cell signaling. Finally, we show how mitochondrial uncoupling could be used to treat several human diseases, such as obesity, cardiovascular diseases, or neurological disorders.

Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases