Dynamic regulation of mitochondrial genome maintenance in germ cells
- PDF / 486,838 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 24 Downloads / 176 Views
REVIEW ARTICLE
Dynamic regulation of mitochondrial genome maintenance in germ cells Katsumi Kasashima • Yasumitsu Nagao Hitoshi Endo
•
Received: 23 May 2013 / Accepted: 4 July 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Mitochondria play a crucial role in the development and function of germ cells. Mitochondria contain a maternally inherited genome that should be transmitted to offspring without reactive oxygen species-induced damage during germ line development. Germ cells are also involved in the mitochondrial DNA (mtDNA) bottleneck; thus, the appropriate regulation of mtDNA in these cells is very important for this characteristic transmission. In this review, we focused on unique regulation of the mitochondrial genome in animal germ cells; paternal elimination and the mtDNA bottleneck in females. We also summarized the mitochondrial nucleoid factors involved in various mtDNA regulation pathways. Among them, mitochondrial transcription factor A (TFAM), which has pleiotropic and essential roles in mtDNA maintenance, appears to have putative roles in germ cell regulation. Keywords Bottleneck Maternal inheritance Mitochondrial DNA Nucleoid TFAM
Introduction The mitochondrion, which is referred to as the ‘cellular power plant’, is an intracellular organelle that produces the majority of cellular ATP through oxidative phosphorylation. Besides this function, mitochondria are also important K. Kasashima H. Endo (&) Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: [email protected] Y. Nagao Center for Experimental Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
for the induction of apoptosis, and generate reactive oxygen species (ROS) by respiration. Mitochondria contain their own genomic DNA called mitochondrial DNA (mtDNA) [1]. In animals, mtDNA exists in multiple copies per cell ([1000 copies), and is maternally inherited from egg cells [2]. Human mtDNA is a 16.6 kb circular doublestranded DNA that encodes 13 proteins, which are components of respiratory chain subunits. mtDNA-encoded proteins are translated through mitochondrial ribosomes, and their expression is essential for respiratory function. Germ cells are essential for the generation of offspring and need to be protected from the accumulation of damaged mtDNA due to ROS. Respiration activity was shown to be suppressed in Xenopus oocytes and the resultant reduced levels of ROS have been suggested to enable accurate mtDNA transmission between generations [3]. It has recently been clarified that mitochondrial genomes and their products (including ribosomal RNA) play important roles in the formation and development of germ cells [4–7], which makes the mitochondrial genome the target for reproductive technology. Mitochondrial transfer (mtDNA replacement) has been attempted as a germline gene therapy for mitochondrial diseases [8] and the efficient development of aged oocytes [9]. However, mitochondrial tra
Data Loading...
