Brandt 2013 Abstract MiP2013

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Brandt T, Mourier A, Stewart JB, Larsson NG, Kühlbrandt W (2013) Structure and function of aged mouse mitochondria. Mitochondr Physiol Network 18.08.
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Brandt T, Mourier A, Stewart JB, Larsson NG, Kuehlbrandt W (2013)

Event: MiPNet18.08_MiP2013

Mitochondria are the energy-converting cell organelles. Their dysfunction has been described as a cause or symptom of ageing. Mutations of mitochondrial DNA lead to respiratory system defects, possibly causing an increased release of reactive oxygen species. Affected cells accumulate, resulting in tissues with mosaic respiratory system deficiency that impairs the efficiency of affected organs [1].

We have previously found dramatic morphological changes in mitochondria of the fast-ageing model organism Podospora anserina [2]. Here, we investigated the morphology and function of aged mammalian mitochondria. We used mouse models that would reveal changes in mitochondrial structure and function in dependence of organismal age. Mitochondrial morphology was examined by electron cryo-tomography, and function was assessed by respirometry in parallel experiments. Thus, in contrast to electron microscopy of resin-embedded samples, we were able to obtain three-dimensional volumes of mitochondria at higher resolution in a close-to-native state, and to correlate our findings to respiratory activity.

We analysed isolated mitochondria from heart, kidney and liver tissue of young and aged mice. Interestingly, we observed clear tissue-specific differences. Whereas heart mitochondria were functionally and structurally unchanged in aged animals, mitochondria from old mouse kidney and liver showed increased populations with altered cristae morphology. Furthermore, we analysed samples from the mtDNA mutator mouse, an established ageing model. In these animals, the highly mutated mitochondrial DNA caused a wide range of structural defects that were accompanied by loss of function.

In summary, mouse mitochondria show subtle, tissue-dependent age-related changes, the molecular causes of which remain to be elaborated. In contrast to a fungal ageing model, a drastic rearrangement of the mitochondrial inner membrane was not observed.


O2k-Network Lab: DE Cologne Larsson NG


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Heart, Liver, Kidney  Preparation: Isolated mitochondria 


Coupling state: OXPHOS 

HRR: Oxygraph-2k 

MiP2013, S09 

Affiliations and author contributions

1 - Dept of Structural Biology, Max-Planck-Institute of Biophysics, Frankfurt am Main, Germany;

2 - Dept of Mitochondrial Biology, Max-Planck-Institute for Biology of Ageing, Cologne, Germany.

Email: tobias.brandt@biophys.mpg.de


References

  1. Larsson NG (2010) Somatic mitochondrial DNA mutations in mammalian aging. Ann Rev Biochem 79: 683-706.
  2. Brust D, Daum B, Breunig C, Hamann A, Kuhlbrandt W, Osiewacz HD (2010) Cyclophilin D links programmed cell death and organismal aging in Podospora anserina. Aging Cell 9: 761-775.