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Sci Rep. 2017 Sep 12;7(1):11257. doi: 10.1038/s41598-017-10843-8.

Live imaging reveals the dynamics and regulation of mitochondrial nucleoids during the cell cycle in Fucci2-HeLa cells.

Author information

1
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602, Japan.
2
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan.
3
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602, Japan. narie@bio.nagoya-u.ac.jp.

Abstract

Mitochondrial DNA (mtDNA) is organized in nucleoprotein complexes called mitochondrial nucleoids (mt-nucleoids), which are critical units of mtDNA replication and transmission. In humans, several hundreds of mt-nucleoids exist in a cell. However, how numerous mt-nucleoids are maintained during the cell cycle remains elusive, because cell cycle synchronization procedures affect mtDNA replication. Here, we analyzed regulation of the maintenance of mt-nucleoids in the cell cycle, using a fluorescent cell cycle indicator, Fucci2. Live imaging of mt-nucleoids with higher temporal resolution showed frequent attachment and detachment of mt-nucleoids throughout the cell cycle. TFAM, an mtDNA packaging protein, was involved in the regulation of this dynamic process, which was important for maintaining proper mt-nucleoid number. Both an increase in mt-nucleoid number and activation of mtDNA replication occurred during S phase. To increase mt-nucleoid number, mtDNA replication, but not nuclear DNA replication, was necessary. We propose that these dynamic and regulatory processes in the cell cycle maintain several hundred mt-nucleoids in proliferating cells.

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