Brandt 2013 Abstract MiP2013

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: 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, liver mitochondria showed a significant increase in structural features attributable to oxidative damage. Old kidney mitochondria showed increased populations of mitochondria 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. Our data suggest that vital mammalian tissues age at different rates, possibly because their mitochondria are differently affected by oxidative damage.

• O2k-Network Lab: DE Cologne Larsson NG

Labels:

Stress:Aging; Senescence"Aging; Senescence" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Mouse  Tissue;cell: Heart, Liver, Kidney  Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. 

HRR: Oxygraph-2k 

Mitochondrial morphology 

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: [email protected]

References

1. Larsson NG (2010) Somatic mitochondrial DNA mutations in mammalian aging. Ann Rev Biochem 79: 683-706.

1. 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.