Mitochondrial uncoupling proteins and phylogenesis – UCP4 as the ancestral uncoupling protein

Abstract

We searched for the previously defined uncoupling protein (UCP) signatures [Jez ek, P. and Urbänkovä, E. (2000) IUBMB Life 49, 63^70] in genomes of Drosophila melanogaster, Caenorhabditis elegans, Dictyostelium discoideum, and Arabidopsis thaliana. We identified four UCPs in Drosophila and one in Caenorhabditis or Dictyostelium as close relatives of human UCP4 (BMCP), but distant from UCP1, UCP2, UCP3, and two plant UCPs of Arabidopsis. But the third Arabidopsis UCP is the closest UCP4 relative. This suggests that UCP4 represents the ancestral UCP from which other mammalian and plant UCPs diverged. Speculations on UCP4 participation in apoptosis are thus supported by its early phylogenetic occurrence. ß

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

“…Thus, our amino acid sequence analysis confirmed the existence of UCP protein (UCP4) in G. cocquereliana mitochondria and suggests a structural similarity and close molecular relationship for this protein to mammalian and other insect UCPs, especially to UCP4 isoforms. Moreover, our results support the annotation that insect UCPs appear to be more closely related to vertebrate UCP4s than to other vertebrate or invertebrate UCPs and that UCP4 might be the ancestral UCP from which other mammalian and plant UCPs diverged (Hanak and Jezek 2001;Jezek 2002).…”

“…Xenopus laevis UCP4 is present in all subdivisions of the brain and has a very high level of expression in peripheral tissues such as liver and kidney (Keller et al 2005). The peripheral tissue distribution of X. laevis UCP4 reinforces the hypothesis that UCP4 might be the ancestral UCP form from which other UCPs diverged (Hanak and Jezek 2001;Keller et al 2005). On the other hand, a phylogenetic analysis by Sokolova and Sokolov (2005) suggests an early evolutionary divergence of UCPs and at least three clades in invertebrates, closely related to vertebrate UCP1-3, UCP4, and UCP5, respectively.…”

“…The evolution of UCP isoforms is under debate. Hanak and Jezek (2001) proposed that UCP4 represents an ancestral UCP form for all UCPs and that UCP1-3 developed later during evolution. Their phylogenetic analysis suggests that invertebrate UCPs, like those of Drosophila melanogaster and Caenorhabditis elegans, are closely related to vertebrate UCP4.…”

Superoxide Stimulates a Proton Leak in Potato Mitochondria That Is Related to the Activity of Uncoupling Protein

“…At this stage, it is not possible to say whether all UCPs will turn out to be involved in reducing reactive oxygen species production. The Arabidopsis genome contains four putative UCP genes (37), and it is likely that some of these genes may play a different role. Intriguingly, UCP genes from monocotyledenous plants do not appear to be induced by low temperature (16,17), which may indicate that UCP is not the main mechanism for avoiding mitochondrial oxidative stress in such plants.…”

Activating ω-6 Polyunsaturated Fatty Acids and Inhibitory Purine Nucleotides Are High Affinity Ligands for Novel Mitochondrial Uncoupling Proteins UCP2 and UCP3

“…predominantly muscle-specific UCP3 and brain-specific UCP4, and BMCP (or UCP5) form a gene subfamily within the mitochondrial anion carrier gene family together with "classic," brown adipose tissue-specific UCP1 and at least three distinct plant UCPs (1,2). Three basic physiological roles of all UCPs should be manifested as consequences of low uncoupling states (2): (i) a slight acceleration of metabolism caused by slightly increased respiration, (ii) a concomitant reduction in reactive oxygen species (ROS) formation (3,4), and (iii) inevitably related, mild thermogenesis.…”