ArticleCell metabolism2019
Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy.
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Metabolic regulation of oocyte maturation and early embryo development in mammals.Life metabolism · 2026Review
- Inheritance and selection of the mitochondrial genome.Nature reviews. Genetics · 2026Review
- Optimal Organelle Inheritance Strategies Under Different Changing Environments and Mutational Pressures.Genome biology and evolution · 2026Article
- Targeting mtDNA to Modulate Mitochondrial Dysfunction in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages.Immunity · 2026Article
- Structural diversity and evolutionary constraints of oxidative phosphorylation.Cell genomics · 2025Article
- Article
- Evolution and maintenance of mtDNA gene content across eukaryotes.The Biochemical journal · 2024Review
- Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders.Cell & bioscience · 2024Review
- Mitochondria makeover: unlocking the path to healthy longevity.Expert opinion on therapeutic targets · 2024Article
- MtDNA deletions and aging.Frontiers in aging · 2024Review
- Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions.Frontiers in endocrinology · 2024Review
- Heteroplasmy and Individual Mitogene Pools: Characteristics and Potential Roles in Ecological Studies.Biology · 2023Review
- Article
- Article
- Mitochondria on the move: Horizontal mitochondrial transfer in disease and health.The Journal of cell biology · 2023Article
- Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023Review
- Mitochondrial Inheritance Following Nuclear Transfer: From Cloned Animals to Patients with Mitochondrial Disease.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Combination of common mtDNA variants results in mitochondrial dysfunction and a connective tissue dysregulation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-to-offspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission.
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