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Within each of our cells, the genetic control of metabolism is split between the nuclear genome and thousands of small, circular mitochondrial genomes. The co-regulation of these two genomes is required for aerobic life, yet paradoxically, their replication and inheritance are uncoupled. Defects in mitochondrial DNA cause hereditary metabolic diseases that impact tissues with high energy demand such as the brain, muscle and heart and are also linked to cancer and the innate immune response. We aim to reveal the mechanisms that ensure mtDNA integrity and inheritance in metazoans, using quantitative imaging, genetics and systems biology approaches.
Mitochondrial DNA encodes functional RNAs and proteins that are critical for the synthesis of adenosine triphosphate or ATP - the chemical currency the must be spent for cellular growth or repair. Every animal cell contains many many copies of mtDNA that are replicated asynchronously, without regard for the nuclear cell cycle. How mtDNA replication is regulated is not well understood, though proper mtDNA replication is key to maintaining a characteristic number of mtDNA copies in highly proliferative tissues, like bone marrow or placenta, as well as in post-mitotic tissues, like the brain, where mitochondrial biogenesis and turnover continue.
Within each of our cells, the genetic control of metabolism is split between the nuclear genome and thousands of small, circular mitochondrial genomes. The co-regulation of these two genomes is required for aerobic life, yet paradoxically, their replication and inheritance are uncoupled. Defects in mitochondrial DNA cause hereditary metabolic diseases that impact tissues with high energy demand such as the brain, muscle and heart and are also linked to cancer and the innate immune response. We aim to reveal the mechanisms that ensure mtDNA integrity and inheritance in metazoans, using quantitative imaging, genetics and systems biology approaches.
Mitochondrial DNA encodes functional RNAs and proteins that are critical for the synthesis of adenosine triphosphate or ATP - the chemical currency the must be spent for cellular growth or repair. Every animal cell contains many many copies of mtDNA that are replicated asynchronously, without regard for the nuclear cell cycle. How mtDNA replication is regulated is not well understood, though proper mtDNA replication is key to maintaining a characteristic number of mtDNA copies in highly proliferative tissues, like bone marrow or placenta, as well as in post-mitotic tissues, like the brain, where mitochondrial biogenesis and turnover continue.
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John A. Smolka,Samantha C. Lewis
Methods in molecular biology (Clifton, N.J.) (2023): 99-106
Methods in cell biology (2021): 39-57
Geneticano. 5 (2010): 611-615
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