Quality control of mitochondria during aging: is there a good and a bad side of mitochondrial dynamics?
Maintenance of functional mitochondria is essential in order to prevent degenerative processes leading to disease and aging. Mitochondrial dynamics plays a crucial role in ensuring mitochondrial quality but may also generate and spread molecular damage through a population of mitochondria. Computational simulations suggest that this dynamics is advantageous when mitochondria are not or only marginally damaged. In contrast, at a higher degree of damage, mitochondrial dynamics may be disadvantageous. Deceleration of fusion-fission cycles could be one way to adapt to this situation and to delay a further decline in mitochondrial quality. However, this adaptive response makes the mitochondrial network more vulnerable to additional molecular damage. The "mitochondrial infectious damage adaptation" (MIDA) model explains a number of inconsistent and counterintuitive data such as the "clonal expansion" of mutant mitochondrial DNA. We propose that mitochondrial dynamics is a double-edged sword and suggest ways to test this experimentally.
Applied Systems Biology, HKI-Center for Systems Biology of Infection, Leibniz-Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute and Friedrich Schiller University, Jena, Germany. thilo.figge@hki-jena.de
Marc Thilo
MT
Figge
Heinz D
HD
Osiewacz
Andreas S
AS
Reichert
D000375:Aging / Q000502:physiology*; D000818:Animals; D003198:Computer Simulation; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000235:genetics; D063154:Mitochondrial Dynamics / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species