Quality matters: how does mitochondrial network dynamics and quality control impact on mtDNA integrity?
Open accessAbstract
Mammalian mtDNA encodes for 13 core proteins of oxidative phosphorylation. Mitochondrial DNA mutations and deletions cause severe myopathies and neuromuscular diseases. Thus, the integrity of mtDNA is pivotal for cell survival and health of the organism. We here discuss the possible impact of mitochondrial fusion and fission on mtDNA maintenance as well as positive and negative selection processes. Our focus is centred on the important question of how the quality of mtDNA nucleoids can be assured when selection and mitochondrial quality control works on functional and physiological phenotypes constituted by oxidative phosphorylation proteins. The organelle control theory suggests a link between phenotype and nucleoid genotype. This is discussed in the light of new results presented here showing that mitochondrial transcription factor A/nucleoids are restricted in their intramitochondrial mobility and probably have a limited sphere of influence. Together with recent published work on mitochondrial and mtDNA heteroplasmy dynamics, these data suggest first, that single mitochondria might well be internally heterogeneous and second, that nucleoid genotypes might be linked to local phenotypes (although the link might often be leaky). We discuss how random or site-specific mitochondrial fission can isolate dysfunctional parts and enable their elimination by mitophagy, stressing the importance of fission in the process of mtDNA quality control. The role of fusion is more multifaceted and less understood in this context, but the mixing and equilibration of matrix content might be one of its important functions.
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Mitochondrial dynamics are an important determinant of organelle quality control and maintenance of genome integrity.
“Mitochondrial dynamics are another important determinant of organelle quality control and the maintenance of genome integrity by facilitating the renewal of healthy mitochondria and the removal of unhealthy/damaged organelles. (Busch, Kowald, and Spelbrink 2014)”
From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as Busch et al. 2014
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The role of mitochondria in mood disorders: from physiology to pathophysiology and to treatment
Giménez-Palomo, A., Dodd, S., Anmella, G., Carvalho, A. F., Scaini, G., Quevedo, J., Pacchiarotti, I., Vieta, E., & Berk, M. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.546801 · Cited by 140 · see citing works
- Authors
- Busch, K. B., Kowald, A., & Spelbrink, J. N.
- Affiliations
- Osnabrück University (DE)
- Newcastle University (GB)
- Radboud University Medical Center (NL)
- Corresponding author
- Spelbrink, Johannes N.
- Venue
- Philosophical Transactions of the Royal Society B Biological Sciences
- Publisher
- The Royal Society
- Published
- 2014-07-05
- Volume
- 369
- Issue
- 1646
- Pages
- 20130442
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC4032518
- OpenAlex
- W2132130208
- Cited by
- 87
- References
- 100
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 1 · 2019: 12 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 4
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (865.10.004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial DNA integrity, mitochondrial fusion, mitochondrial fission, mitochondrial quality control, mitochondrial heteroplasmy, mitochondrial DNA deletions, mitochondrial DNA mutations, TFAM, mitophagy, oxidative phosphorylation, mitochondrial heterogeneity, myopathy, neuromuscular disorders
- MeSH terms
- DNA, Mitochondrial, Humans, Mitochondria, Selection, Genetic, Mitochondrial Proteins, Mitophagy
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