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Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1)

Author:
Ježek, Petr, Jabůrek, Martin, Porter, Richard K.
Source:
Biochimica et biophysica acta 2019 v.1860 no.3 pp. 259-269
ISSN:
0005-2728
Subject:
anions, biogenesis, brown adipose tissue, fatty acids, heat production, mammals, mitochondria, models, post-translational modification
Abstract:
Brown adipose tissue (BAT) and brown in white (brite) adipose tissue, termed also beige adipose tissue, are major sites of mammalian nonshivering thermogenesis. Mitochondrial uncoupling protein 1 (UCP1), specific for these tissues, is the key factor for heat production. Recent molecular aspects of UCP1 structure provide support for the fatty acid cycling model of coupling, i.e. when UCP1 expels fatty acid anions in a uniport mode from the matrix, while uncoupling. Protonophoretic function is ensured by return of the protonated fatty acid to the matrix independent of UCP1. This mechanism is advantageous for mitochondrial uncoupling and compatible with heat production in a pro-thermogenic environment, such as BAT. It must still be verified whether posttranslational modification of UCP1, such as sulfenylation of Cys253, linked to redox activity, promotes UCP1 activity. BAT biogenesis and UCP1 expression, has also been linked to the pro-oxidant state of mitochondria, further endorsing a redox signalling link promoting an establishment of pro-thermogenic state. We discuss circumstances under which promotion of superoxide formation exceeds its attenuation by uncoupling in mitochondria and throughout point out areas of future research into UCP1 function.
Agid:
6225353