Weber 2013 Abstract MiP2013

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Weber RE (2013) Hemoglobins: Molecular adaptations safeguarding mitochondrial O2 supply. Mitochondr Physiol Network 18.08.
Link:
Roy E Weber
MiP2013, Book of Abstracts Open Access

Weber RE (2013)

Event: MiPNet18.08_MiP2013

Kjell Johansen lecture

Vertebrate hemoglobins (Hb) are exquisitely designed to transport O2 from the respiratory organs to the tissues, thereby safeguarding mitochondrial O2 supply and aerobic metabolism in the face of wide and independent variations in O2 tensions and temperature at the sites for loading and unloading of O2 [1-3].

In transporting O2, vertebrate Hbs (composed of 2 α and 2 β globin chains) switch between the T (tense, low O2-affinity, deoxygenated) structure that predominates in the tissues, and the R (relaxed, high-affinity, oxygenated) structure that predominates in the lungs and gills. The T-R shift is basic to cooperativity between the O2-binding heme groups that increases O2 (un)loading for a given change in O2 tension - and is reflected in the sigmoid shape of O2 binding curves. Hb’s in vivo O2 binding properties are a product of its intrinsic O2 affinity and its interaction with red cell allosteric effectors that decreases Hb-O2 affinity by stabilizing the T-structure. Apart from protons and CO2 (that facilitate O2 unloading in the acid tissues via the “Bohr-effect”) these effectors include chloride ions and organic phosphates [ATP in lower vertebrates, IPP (inositol pentaphosphate) in birds and DPG (diphosphoglycerate) in mammals]. The interaction with effectors varies between and within individual species and plays a key role in adjusting O2 transport in response to changes in environmental conditions, metabolic requirements, and mode of life. The decrease in Hb-O2 affinity with rising temperature mandated by the exothermic nature of heme oxygenation, enhances O2 unloading in warm tissues that require more O2, but may become maladaptive – and thus commonly is reduced - in regional heterothermic species where it may hamper O2 unloading (in cold extremities of arctic mammals) or cause excessive O2 release (in warm muscles, brains or eyes of fast-swimming fish).

Based on case studies (Hbs from estivating fish, fast-swimming gamefish, high-altitude Andean frogs, geese that scale the Himalayas, Rocky Mountain Deer mice and Hb recreated from extinct mammoths [4-6]) the treatise analyses the molecular mechanisms for Hb’s role in securing mitochondrial O2 supply under stressful conditions - illustrating the key significance of molecular interactions to understanding physiological ecology.

Keywords: Hemoglobin


Labels: MiParea: Comparative MiP;environmental MiP 


Organism: Other mammals, Birds, Amphibians, Fishes  Tissue;cell: Blood cells  Preparation: Intact organism 

Regulation: Oxygen kinetics, Temperature 



Additional: MiP2013 

Affiliations and author contributions

1 - Zoophysiology, Department of Bioscience, Aarhus University, Denmark. - Email: roy.weber@biology.au.dk

References

  1. Johansen K, Weber RE (1976) On the adaptability of haemoglobin function to environmental conditions. In Spencer Davies P (ed): Perspectives in Experimental Biology, Vol 1, Zoology. Oxford, Pergamon Press: 219-234.
  2. Weber RE, Fago A (2004) Functional adaptation and its molecular basis in vertebrate hemoglobins, neuroglobins and cytoglobins. Respir Physiol Neurobiol 144: 141-159.
  3. Mairbaurl H, Weber RE (2012) Oxygen transport by hemoglobin. Compr Physiol 2: 1463-1489.
  4. Weber RE (2007) High-altitude adaptations in vertebrate hemoglobins. Respir Physiol Neurobiol 158: 132-142.
  5. Storz JF, Runck AM, Sabatino SJ, Kelly JK, Ferrand N, Moriyama H, Weber RE, Fago A (2009) Evolutionary and functional insights into the mechanism underlying high-altitude adaptation of deer mouse hemoglobin. Proc Natl Acad Sci U S A 144: 14450-14455.
  6. Weber RE, Campbell KL (2011) Temperature dependence of haemoglobin-oxygen affinity in heterothermic vertebrates: mechanisms and biological significance. Acta Physiol 202: 549-562.


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