Deceleration of fusion-fission cycles improves mitochondrial quality control during aging.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractMitochondrial dynamics and mitophagy play a key role in ensuring mitochondrial quality control. Impairment thereof was proposed to be causative to neurodegenerative diseases, diabetes, and cancer. Accumulation of mitochondrial dysfunction was further linked to aging. Here we applied a probabilistic modeling approach integrating our current knowledge on mitochondrial biology allowing us to simulate mitochondrial function and quality control during aging in silico. We demonstrate that cycles of fusion and fission and mitophagy indeed are essential for ensuring a high average quality of mitochondria, even under conditions in which random molecular damage is present. Prompted by earlier observations that mitochondrial fission itself can cause a partial drop in mitochondrial membrane potential, we tested the consequences of mitochondrial dynamics being harmful on its own. Next to directly impairing mitochondrial function, pre-existing molecular damage may be propagated and enhanced across the mitochondrial population by content mixing. In this situation, such an infection-like phenomenon impairs mitochondrial quality control progressively. However, when imposing an age-dependent deceleration of cycles of fusion and fission, we observe a delay in the loss of average quality of mitochondria. This provides a rational why fusion and fission rates are reduced during aging and why loss of a mitochondrial fission factor can extend life span in fungi. We propose the 'mitochondrial infectious damage adaptation' (MIDA) model according to which a deceleration of fusion-fission cycles reflects a systemic adaptation increasing life span.
CitationDeceleration of fusion-fission cycles improves mitochondrial quality control during aging. 2012, 8 (6):e1002576 PLoS Comput. Biol.
AffiliationApplied Systems Biology, Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute and Friedrich Schiller University, Jena, Germany.
JournalPLoS computational biology
The following license files are associated with this item:
- Quality control of mitochondria during aging: is there a good and a bad side of mitochondrial dynamics?
- Authors: Figge MT, Osiewacz HD, Reichert AS
- Issue date: 2013 Apr
- The systems biology of mitochondrial fission and fusion and implications for disease and aging.
- Authors: Chauhan A, Vera J, Wolkenhauer O
- Issue date: 2014 Feb
- Fission and selective fusion govern mitochondrial segregation and elimination by autophagy.
- Authors: Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS
- Issue date: 2008 Jan 23
- Mitochondrial dynamics--fusion, fission, movement, and mitophagy--in neurodegenerative diseases.
- Authors: Chen H, Chan DC
- Issue date: 2009 Oct 15
- Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view.
- Authors: Twig G, Hyde B, Shirihai OS
- Issue date: 2008 Sep