Chakrabarti 2017 Abstract MITOEAGLE Barcelona

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COST Action MITOEAGLE

Mitochondrial lipids and proteomics - comparative studies in mammalian ageing. Chakrabarti_Presentation

Link: MitoEAGLE

Chakrabarti L (2017)

Event: MitoEAGLE Barcelona 2017

COST Action MITOEAGLE

Our group is interested in understanding how the mitochondrion changes with age. Our approaches are largely biochemical with a component of ‘omics’ work for global measurements[1,2]. Recently we have been working on mitochondrial ageing viewed from a variety of different angles, I will list these here and expand on them at the meeting.

Correlating mitochondrial proteomic ageing in health and neurodegeneration can potentially reveal protective changes versus dysfunctional events. We have looked at the proteome of a mouse model of neurodegeneration (pcd) and been able to match the changes in the model with those that occur in normal mammalian ageing and also in Parkinson’s disease. A particularly interesting find is the protein haemoglobin which may have an important role in maintaining mitochondrial oxygen content[3,4,5].

In a simple study we looked again at the complex 1 activity in pcd mouse brain regions compared with age matched unaffected littermates and strain matched older mice[6]. We concluded that complex 1 decreases in all brain regions with age and also in a region specific manner with neurodegeneration, regardless of age.

A set of three ongoing interlinked experiments are providing some good insight into the crosstalk between lipids and proteins in mitochondria from the brain and muscle. We are looking at the responses due to ageing. The proteome of the muscle and brain mitochondria show some interesting, particularly carbonic anhydrases which we show to be elevated in ageing[7]. We have also found that the mitochondrial lipidome is changed in such a characteristic manner with age, that mitochondrial lipid profiles define mammalian tissue and age. The third of these studies examines the mitochondrial proteome and lipidome in the mouse and the Pipistrelle bat. These are two mammals with similar size and metabolic rate but very different maximal lifespans, the bat being exceptionally long-lived. Having found some mitochondrial targets and pathways we are now testing these in various systems with some different interventions. These include human neurodegeneration (Alzheimer’s and Parkinson’s disease), lifespan studies in the nematode worm, hypoxia and or exercise training in fruit flies. Our aim is to manipulate mitochondrial populations so they can be returned to a more youthful state.


Bioblast editor: Kandolf G


Labels: MiParea: Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style  Pathology: Aging;senescence, Neurodegenerative, Parkinson's  Stress:Oxidative stress;RONS  Organism: Mouse, Drosophila, Caenorhabditis elegans, Nematodes  Tissue;cell: Nervous system 

Enzyme: Complex I 



Event: A3 


Affiliations

Univ Nottingham, UK.

References

  1. Chakrabarti L, Zahra R, Jackson SM, Kazemi-Esfarjani P, Sopher BL, Mason AG, Toneff T, Ryu S, Shaffer S, Kansy JW, Eng J, Merrihew G, MacCoss MJ, Murphy A, Goodlett DR, Hook V, Bennett CL, Pallanck LJ, La Spada AR (2010) Mitochondrial dysfunction in NnaD mutant flies and Purkinje cell degeneration (pcd) mice reveals a role for Nna proteins in neuronal bioenergetics. Neuron 66:835-47.
  2. Ingram T, Chakrabarti L (2016) Proteomic profiling of mitochondria: what does it tell us about the ageing brain? Aging (Albany NY). doi:10.18632/aging.101131.
  3. Shephard F, Greville-Heygate O, Marsh O, Anderson S, Chakrabarti LA (2013) Mitochondrial location for haemoglobins-Dynamic distribution in ageing and Parkinson’s disease. Mitochondrion 14:64–72.
  4. Shephard F, Greville-Heygate O, Liddell S, Emes R, Chakrabarti L (2016) Analysis of Mitochondrial haemoglobin in Parkinson’s disease brain. Mitochondrion 29:45–52.
  5. Freed J, Chakrabarti L (2016) Defining a role for hemoglobin in Parkinson’s disease. npj Park. Dis 2:16021.
  6. Pollard AK, Craig EL, Chakrabarti L (2016) Mitochondrial Complex 1 activity measured by spectrophotometry is reduced across all brain regions in ageing and more specifically in neurodegeneration. (2016) PLoS One 11:e0157405.
  7. Pollard A, Shephard F, Freed J, Liddell S (2016) Chakrabarti L Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. Aging (Albany NY) 8:2425-36.