English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Mutations of mitochondrial DNA are not major contributors to aging of fruit flies

MPS-Authors
/persons/resource/persons129390

Kauppila,  T. E. S.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129386

Bratic,  A.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129382

Baggio,  F.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129348

Partridge,  L.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons15150

Grönke,  S.
Department of Molecular Developmental Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons129342

Larsson,  N.G.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

External Resource
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Kauppila, T. E. S., Bratic, A., Jensen, M. B., Baggio, F., Partridge, L., Jasper, H., et al. (2018). Mutations of mitochondrial DNA are not major contributors to aging of fruit flies. Proc Natl Acad Sci U S A, 115(41), E9620-E9629. doi:10.1073/pnas.1721683115.


Cite as: https://hdl.handle.net/21.11116/0000-000B-47CF-D
Abstract
Mammals develop age-associated clonal expansion of somatic mtDNA mutations resulting in severe respiratory chain deficiency in a subset of cells in a variety of tissues. Both mathematical modeling based on descriptive data from humans and experimental data from mtDNA mutator mice suggest that the somatic mutations are formed early in life and then undergo mitotic segregation during adult life to reach very high levels in certain cells. To address whether mtDNA mutations have a universal effect on aging metazoans, we investigated their role in physiology and aging of fruit flies. To this end, we utilized genetically engineered flies expressing mutant versions of the catalytic subunit of mitochondrial DNA polymerase (DmPOLgammaA) as a means to introduce mtDNA mutations. We report here that lifespan and health in fruit flies are remarkably tolerant to mtDNA mutations. Our results show that the short lifespan and wide genetic bottleneck of fruit flies are limiting the extent of clonal expansion of mtDNA mutations both in individuals and between generations. However, an increase of mtDNA mutations to very high levels caused sensitivity to mechanical and starvation stress, intestinal stem cell dysfunction, and reduced lifespan under standard conditions. In addition, the effects of dietary restriction, widely considered beneficial for organismal health, were attenuated in flies with very high levels of mtDNA mutations.