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Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA
Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA
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Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA
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Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA
Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA
Journal Article

Human RCC1L is involved in the maintenance of mitochondrial nucleoids and mtDNA

2025
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Overview
Mitochondrial DNA (mtDNA) is organized with proteins into mitochondrial nucleoid (mt-nucleoid). The mt-nucleoid is a unit for the maintenance and function of mtDNA. The regulator of chromosome condensation 1-like protein (RCC1L) performs various functions in mitochondria, including translation, but its involvement in regulating mt-nucleoid maintenance is unknown. Herein, we found that human RCC1L was required to maintain mt-nucleoids and mtDNA. Human RCC1L has three splicing isoforms: RCC1L V1 , RCC1L V2 , and RCC1L V3 . Knockout (KO) cells lacking all RCC1L isoforms, which were lethal without pyruvate and uridine, exhibited a decrease in mt-nucleoids and mtDNA, along with swollen and fragmented mitochondria. Among the three RCC1L isoforms, only RCC1L V1 recovered all phenotypes observed in RCC1L KO cells. As the treatment of wild-type cells with chloramphenicol, a mitochondrial translation inhibitor, did not lead to the decrease in mt-nucleoids accompanied by mtDNA depletion, the decrease in mt-nucleoids and mtDNA in RCC1L KO cells was not solely attributed to impaired mitochondrial translation. Using conditional RCC1L KO cells, we observed a rapid decrease in mt-nucleoids and mtDNA during a specific period following RCC1L loss. Our findings indicate that RCC1L regulates the maintenance of mt-nucleoids and mtDNA besides its role in mitochondrial translational regulation.

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