Intricacies and surprises of nuclear–mitochondrial co-evolution

Willkomm, Dagmar K.; Hartmann, Roland K.

doi:10.1042/bj20061241

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…Our observation also indicates that most human mitomiRs are not conserved beyond primates, which may suggest a species-specific targeting of miRNAs to human mitochondria. We propose that this biased lack of conservation throughout species likely relates to the peculiar evolutionary pressure that concerns mitochondrial genomes [46] , [47] . We speculate that further investigation specifically on hsa-miR-1974, hsa-miR-1977 and hsa-miR-1978, which are human-specific only may greatly serve our understanding into both the origin and evolution of miRNAs.…”

Section: Discussionmentioning

confidence: 96%

Nuclear Outsourcing of RNA Interference Components to Human Mitochondria

et al. 2011

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MicroRNAs (miRNAs) are small non-coding RNAs that associate with Argonaute proteins to regulate gene expression at the post-transcriptional level in the cytoplasm. However, recent studies have reported that some miRNAs localize to and function in other cellular compartments. Mitochondria harbour their own genetic system that may be a potential site for miRNA mediated post-transcriptional regulation. We aimed at investigating whether nuclear-encoded miRNAs can localize to and function in human mitochondria. To enable identification of mitochondrial-enriched miRNAs, we profiled the mitochondrial and cytosolic RNA fractions from the same HeLa cells by miRNA microarray analysis. Mitochondria were purified using a combination of cell fractionation and immunoisolation, and assessed for the lack of protein and RNA contaminants. We found 57 miRNAs differentially expressed in HeLa mitochondria and cytosol. Of these 57, a signature of 13 nuclear-encoded miRNAs was reproducibly enriched in mitochondrial RNA and validated by RT-PCR for hsa-miR-494, hsa-miR-1275 and hsa-miR-1974. The significance of their mitochondrial localization was investigated by characterizing their genomic context, cross-species conservation and instrinsic features such as their size and thermodynamic parameters. Interestingly, the specificities of mitochondrial versus cytosolic miRNAs were underlined by significantly different structural and thermodynamic parameters. Computational targeting analysis of most mitochondrial miRNAs revealed not only nuclear but also mitochondrial-encoded targets. The functional relevance of miRNAs in mitochondria was supported by the finding of Argonaute 2 localization to mitochondria revealed by immunoblotting and confocal microscopy, and further validated by the co-immunoprecipitation of the mitochondrial transcript COX3. This study provides the first comprehensive view of the localization of RNA interference components to the mitochondria. Our data outline the molecular bases for a novel layer of crosstalk between nucleus and mitochondria through a specific subset of human miRNAs that we termed ‘mitomiRs’.

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Section: Discussionmentioning

confidence: 96%

Nuclear Outsourcing of RNA Interference Components to Human Mitochondria

et al. 2011

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“…The major function of mitochondria in mammalian cells is to generate adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to accommodate cellular energy demands (14,18,51,112). The nucleus represents a less oxidizing and hospitable environment for high fidelity storage of large amounts of genetic material necessary to code for the gene products required for organism function (226). Many mitochondrial functions are shown to be regulated by nuclearencoded proteins and via protein phosphorylation (159).…”

Section: Mitochondrial Activities Guided By Nuclear Genome-encoded Prmentioning

confidence: 99%

Cell Cycle Regulators Guide Mitochondrial Activity in Radiation-Induced Adaptive Response

Alexandrou

2014

Antioxidants & Redox Signaling

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Significance: There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated and remains controversial, LDIR is shown to induce temporary but significant adaptive responses in mammalian cells and animals. The mechanisms guiding the mitochondrial function in LDIR-induced adaptive response represent a unique communication between DNA damage and cellular metabolism. Elucidation of the LDIRregulated mitochondrial activity may reveal new mechanisms adjusting cellular function to cope with hazardous environmental stress. Recent Advances: Key cell cycle regulators, including Cyclin D1/CDK4 and Cyclin B1/ cyclin-dependent kinase 1 (CDK1) complexes, are actively involved in the regulation of mitochondrial functions via phosphorylation of their mitochondrial targets. Accumulating new evidence supports a concept that the Cyclin B1/CDK1 complex acts as a mediator in the cross talk between radiation-induced DNA damage and mitochondrial functions to coordinate cellular responses to low-level genotoxic stresses. Critical Issues: The LDIR-mediated mitochondrial activity via Cyclin B1/CDK1 regulation is an irreplaceable network that is able to harmonize vital cellular functions with adjusted mitochondrial metabolism to enhance cellular homeostasis. Future Directions: Further investigation of the coordinative mechanism that regulates mitochondrial activities in sublethal stress conditions, including LDIR, will reveal new insights of how cells cope with genotoxic injury and will be vital for future targeted therapeutic interventions that reduce environmental injury and cancer risk.

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“…This gain in plasticity may represent an evolutionary process that allows the nuclear-encoded proteins to adapt to the structurally degenerated RNAs from organelles. Evolutionary induced changes in intrinsic properties of proteins, may thus represent an alternative to other strategies, such as those reported for the mitochondrial ribosome, where the strong restriction in RNA sizes is compensated by extension of the number and size of the nuclear encoded proteins (Willkomm and Hartmann 2006). If mt-aaRS do have partner proteins that might also contribute to improved recognition of degenerated tRNAs remains an open question.…”

Section: Unprecedented Plasticity Of Mitochondrial Aarss and Trnasmentioning

confidence: 99%

“…All have lost some information as compared to their bacterial homologs. For instance, mRNAs miss 3′ and 5′ untranslated regions, ribosomal RNAs are significantly shorter than bacterial counterparts and tRNAs present a range of peculiarities, from the absence of a few nucleotide signature motifs to the absence of full structural domains (Willkomm and Hartmann 2006).…”

Section: Introductionmentioning

confidence: 99%

Translation in Mammalian Mitochondria: Order and Disorder Linked to tRNAs and Aminoacyl-tRNA Synthetases

Florentz

Pütz

Jühling

et al. 2013

Translation in Mitochondria and Other Organelles

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Transfer RNAs (tRNAs) and aminoacyl-tRNA synthetases (aaRSs) are key actors in all translation machineries. AaRSs aminoacylate cognate tRNAs with a specific amino acid that is transferred to the growing protein chain on the ribosome. Mammalian mitochondria possess their own translation machinery for the synthesis of 13 proteins only, all subunits of the respiratory chain complexes involved in the synthesis of ATP. While 22 tRNAs and two ribosomal RNAs are also coded by the mitochondrial genome, aaRSs are nuclear encoded and become imported. The fact that the two cellular genomes, nuclear and mitochondrial,

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Intricacies and surprises of nuclear–mitochondrial co-evolution

Cited by 5 publications

References 16 publications

Nuclear Outsourcing of RNA Interference Components to Human Mitochondria

Nuclear Outsourcing of RNA Interference Components to Human Mitochondria

Cell Cycle Regulators Guide Mitochondrial Activity in Radiation-Induced Adaptive Response

Translation in Mammalian Mitochondria: Order and Disorder Linked to tRNAs and Aminoacyl-tRNA Synthetases

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