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Mitochondria–nucleus network for genome stability

Kaniak-Golik, Aneta and Skoneczna, Adrianna (2015) Mitochondria–nucleus network for genome stability. Free Radical Biology & Medicine, 82 . pp. 73-104. ISSN 1873-4596

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Official URL: http://dx.doi.org/10.1016/j.freeradbiomed.2015.01....

Abstract

The proper functioning of the cell depends on preserving the cellular genome. In yeast cells, a limited number of genes are located on mitochondrial DNA. Although the mechanisms underlying nuclear genome maintenance are well understood, much less is known about the mechanisms that ensure mitochondrial genome stability. Mitochondria influence the stability of the nuclear genome and vice versa. Little is known about the two-way communication and mutual influence of the nuclear and mitochondrial genomes. Although the mitochondrial genome replicates independent of the nuclear genome and is organized by a distinct set of mitochondrial nucleoid proteins, nearly all genome stability mechanisms responsible for maintaining the nuclear genome, such as mismatch repair, base excision repair, and double-strand break repair via homologous recombination or the nonhomologous end-joining pathway, also act to protect mitochondrial DNA. In addition to mitochondria-specific DNA polymerase γ, the polymerases α, η, ζ, and Rev1 have been found in this organelle. A nuclear genome instability phenotype results from a failure of various mitochondrial functions, such as an electron transport chain activity breakdown leading to a decrease in ATP production, a reduction in the mitochondrial membrane potential (ΔΨ), and a block in nucleotide and amino acid biosynthesis. The loss of ΔΨ inhibits the production of iron–sulfur prosthetic groups, which impairs the assembly of Fe–S proteins, including those that mediate DNA transactions; disturbs iron homeostasis; leads to oxidative stress; and perturbs wobble tRNA modification and ribosome assembly, thereby affecting translation and leading to proteotoxic stress. In this review, we present the current knowledge of the mechanisms that govern mitochondrial genome maintenance and demonstrate ways in which the impairment of mitochondrial function can affect nuclear genome stability.

Item Type:Article
Uncontrolled Keywords:Genome maintenance,rho0, Oxidative stress, Iron–sulfur cluster, Heme protein, Membrane potential, DNA damage, DNA repair, Protein assembly, Metal toxicit
Subjects:Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology
Divisions:Laboratory of Mutagenesis and DNA Repair
ID Code:903
Deposited By: dr hab. Adrianna Skoneczna
Deposited On:09 Oct 2015 10:14
Last Modified:13 Oct 2015 08:46

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