Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria
By Andriy Fedorenko, P. Lishko, Yuriy Kirichok. Cell, 2012
945 citations recorded by the source corpus.
Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). Upon activation by long-chain fatty acids (LCFAs), UCP1 increases the conductance of the inner mitochondrial membrane (IMM) to make BAT mitochondria generate heat rather than ATP. Despite being a member of the family of mitochondrial anion carriers (SLC25), UCP1 is believed to transport H+ by an unusual mechanism that has long remained unresolved. Here, we achieved direct patch-clamp measurements of UCP1 currents from the IMM of BAT mitochondria. We show that UCP1 is an LCFA anion/H+ symporter. However, the LCFA anions cannot dissociate from UCP1 due to hydrophobic interactions established by their hydrophobic tails, and UCP1 effectively operates as an H+ carrier activated by LCFA. A similar LCFA-dependent mechanism of transmembrane H+ transport may be employed by other SLC25 members and be responsible for mitochondrial uncoupling and regulation of metabolic efficiency in various tissues.
Subfields: Biochemistry, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/be01d40ecce541248b090cb86ed466cad85aa368
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Citations in the corpus
- Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “234 GENES & DEVELOPMENT 27:234–250 2013 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/13; www.genesdev.org chain (ETC) (Krauss et al. 2005; Bartelt et al. 2011; Fedorenko et al. 2012).”
- Adipose tissue plasticity in health and disease (2022, background): “UCP1 function and thus thermogenic respiration is acutely activated by long chain fatty acids (LCFA) and inhibited by purine nucleotides (Bertholet and Kirichok, 2017; Fedorenko et al., 2012).”