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Evolution and functional characterisation of uncoupling proteins in vertebrates
The evolution of UCP1 in vertebrates – a summary This thesis unravels the evolution of UCP1, a crucial protein for heat generation recruited during adaptive NST. In eutherian mammals UCP1 uncouples the respiratory chain from ATP synthesis to dissipate proton motive force as heat but the question...
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| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2007
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| Zusammenfassung: | The evolution of UCP1 in vertebrates – a summary
This thesis unravels the evolution of UCP1, a crucial protein for heat generation recruited during
adaptive NST. In eutherian mammals UCP1 uncouples the respiratory chain from ATP synthesis
to dissipate proton motive force as heat but the question of when the protein emerged during
evolution and what its original function was, has not been resolved.
In the initial studies we show that standard molecular techniques are insufficient to detect UCP1
(Jastroch et al. 2004a, Chapter I) but the phylogeny of UCPs suggests an ancient origin of UCP1
(Jastroch et al. 2004b, Chapter II). The presence of UCP1 in fish demonstrates the emergence of
UCP1 before the divergence of ray-finned and lobe-finned vertebrate lineages 420 MYA
(Jastroch et al. 2005, Chapter III). UCP1 gene regulation in the common carp, Cyprinus carpio,
indicates a physiological role other than heat production but biochemical studies suggests that
carp UCP1 is a functional uncoupling protein with broadly the same activatory and inhibitory
characteristics as eutherian UCP1 (Jastroch et al. 2007, Chapter IV). Studies in marsupials,
which separated from eutherians 150 MYA, demonstrate that in these species transcriptional
control targets UCP1 expression to adipose tissue (Jastroch et al. in preparation, Chapter V). In
the gray short-tailed opossum, Monodelphis domestica, UCP1 is transiently expressed and
restricted to the early development, similar to observations in larger eutherian neonates. In the
fat-tailed dunnart, Sminthopsis crassicaudata, UCP1 is expressed during adulthood and is
elevated in response to cold exposure. Although these experiments suggest the presence of
UCP1-mediated NST, UCP1-dependent thermogenesis in the animal has yet to be shown in
marsupials. However, the identification of a BAT-like tissue provides the molecular basis to
reinvestigate adaptive NST in marsupials. In the phylogenetically ancient afrotherian rock
elephant shrew, Elephantulus myurus, a species that diverged from modern eutherians about 100
MYA, we demonstrate the presence of functional BAT (Mzilikazi, Jastroch, Meyer, and Klingenspor, submitted, Chapter VI). Although NST, BAT and UCP1 are found in E. myurus,
NST does not appear to be adaptive as demonstrated in modern eutherians. While adaptivity of
NST seems not to be required in our experiments, the significance of NST during the seasons of
the mild natural habitats of South Africa remains to be investigated in further studies.
The focus of the thesis is the evolution of UCP1 but I also investigated if UCP3 might have a
thermogenic role in the yellow-footed Antechinus, Antechinus flavipes, a marsupial lacking BAT
(Jastroch et al., in preparation, Chapter VII). A thermogenic function of UCP3, as found for
UCP1, can be excluded by measurements of uncoupling activity in myotubular mitochondria.
However, I found evidence that mild uncoupling mediated by the ANT (adenine nucleotide
translocase) occurs in myotubular mitochondria of cold-acclimated A. flavipes and may play a
role in protection from oxidative stress during cold exposure.
The search for UCPs in vertebrates has resulted in the identification of UCP2 and UCP3 in
different vertebrate groups and might assist to resolve their physiological roles. By comparing
phylogenetic branch lengths and gene regulation, I suggest that in contrast to UCP1, the function
of UCP2 and UCP3 may be well conserved in all vertebrates.
Finally, in order to compare different UCP orthologues and paralogues, we have established cell
lines ectopically expressing mouse UCP1. In isolated mitochondria of this cell system, we
demonstrate native function of mouse UCP1 (Jastroch et al. 2007, BBA, Chapter VIII and
Results and Discussion). This cell system will serve in future studies to compare different UCPs
in the presence of an identical mitochondrial and genetical background. |
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| Umfang: | 193 Seiten |
| DOI: | 10.17192/z2007.0522 |