Deceleration of fusion-fission cycles improves mitochondrial quality control during aging.

2.50
HDL Handle:
http://hdl.handle.net/10033/246151
Title:
Deceleration of fusion-fission cycles improves mitochondrial quality control during aging.
Authors:
Figge, Marc Thilo; Reichert, Andreas S; Meyer-Hermann, Michael; Osiewacz, Heinz D
Abstract:
Mitochondrial 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.
Affiliation:
Applied Systems Biology, Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute and Friedrich Schiller University, Jena, Germany.
Citation:
Deceleration of fusion-fission cycles improves mitochondrial quality control during aging. 2012, 8 (6):e1002576 PLoS Comput. Biol.
Journal:
PLoS computational biology
Issue Date:
Jun-2012
URI:
http://hdl.handle.net/10033/246151
DOI:
10.1371/journal.pcbi.1002576
PubMed ID:
22761564
Type:
Article
Language:
en
ISSN:
1553-7358
Appears in Collections:
publications of the division system immunology (SIMM)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorFigge, Marc Thiloen_GB
dc.contributor.authorReichert, Andreas Sen_GB
dc.contributor.authorMeyer-Hermann, Michaelen_GB
dc.contributor.authorOsiewacz, Heinz Den_GB
dc.date.accessioned2012-09-27T12:32:19Z-
dc.date.available2012-09-27T12:32:19Z-
dc.date.issued2012-06-
dc.identifier.citationDeceleration of fusion-fission cycles improves mitochondrial quality control during aging. 2012, 8 (6):e1002576 PLoS Comput. Biol.en_GB
dc.identifier.issn1553-7358-
dc.identifier.pmid22761564-
dc.identifier.doi10.1371/journal.pcbi.1002576-
dc.identifier.urihttp://hdl.handle.net/10033/246151-
dc.description.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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PLoS computational biologyen_GB
dc.titleDeceleration of fusion-fission cycles improves mitochondrial quality control during aging.en
dc.typeArticleen
dc.contributor.departmentApplied Systems Biology, Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute and Friedrich Schiller University, Jena, Germany.en_GB
dc.identifier.journalPLoS computational biologyen_GB

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.