An explanation of how mutant and wild-type mitochondria might stably co-exist in inherited mitochondrial diseases

Mitochondria are cellular organelles of crucial relevance for the survival of metazoan organisms. Damage to the mitochondrial DNA can give rise to a variety of mitochondrial diseases and is thought also to be involved in the aging process. The fate of mtDNA mutants is controlled by their synthesis a...

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Bibliographic Details
Published in:PNAS nexus 2022-09, Vol.1 (4), p.pgac192-pgac192
Main Authors: Kowald, Axel, Kemeth, Felix P, Kirkwood, Tom B L
Format: Article
Language:English
Subjects:
Biological, Health, and Medical Sciences
Genetic aspects
Health aspects
Mathematical models
Mitochondrial diseases
Mutation (Biology)
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Summary:Mitochondria are cellular organelles of crucial relevance for the survival of metazoan organisms. Damage to the mitochondrial DNA can give rise to a variety of mitochondrial diseases and is thought also to be involved in the aging process. The fate of mtDNA mutants is controlled by their synthesis as well as degradation and mathematical models can help to better understand this complex interplay. We present here a model that combines a replicative advantage for mtDNA mutants with selective degradation enabled by mitochondrial fission and fusion processes. The model not only shows that the cell has efficient means to deal with (many) types of mutants but, surprisingly, also predicts that under certain conditions a stable co-existence of mutant and wild-type mtDNAs is possible. We discuss how this new finding might explain how mitochondria can be at the heart of processes with such different phenotypes as mitochondrial diseases and aging.
ISSN:2752-6542
2752-6542
DOI:10.1093/pnasnexus/pgac192