Coupling of mitochondrial translation with the formation of respiratory complexes in yeast mitochondria.

In contrast to most other eukaryotic organisms, yeast can survive without respiration. This ability has been exploited to investigate nuclear genes required for expression of mitochondrial DNA. Availability of complete Saccharomyces cerevisiae genomic sequence has provided additional help in detailed molecular analysis. Seven of the eight major products encoded by mitochondrial DNA are hydrophobic subunits of respiratory complexes in the inner membrane. Localization of the translation process in the same cellular compartment ensures synthesis of mitochondrially encoded proteins near sites of their assembly into multimeric respiratory complexes. Association of mitochondrial ribosomes with the membrane is mediated by mRNA-specific translational activators, that are involved in the recognition of initiation codon. The newly synthesized mitochondrial proteins are transferred to membrane by a specific export system. This review discusses the role of membrane-localized factors responsible for quality control and turnover of mitochondrially synthesized subunits as well as for assembly of respiratory complexes.

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Complete Repopulation of Mouse Mitochondrial DNA-less Cells With Rat Mitochondrial DNA Restores Mitochondrial Translation but Not Mitochondrial Respiratory Function

Genetics ◽

10.1093/genetics/155.1.301 ◽

2000 ◽

Vol 155 (1) ◽

pp. 301-307 ◽

Cited By ~ 1

Author(s):

Makiko Yamaoka ◽

Kotoyo Isobe ◽

Hiroshi Shitara ◽

Hiromichi Yonekawa ◽

Shigeaki Miyabayashi ◽

...

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Dysfunction ◽

Nuclear Dna ◽

Living Cells ◽

Mitochondrial Genomes ◽

Mus Musculus Domesticus ◽

Mitochondrial Translation ◽

Respiratory Complexes ◽

Mouse Species ◽

Mitochondrial Respiratory

Abstract By the fusion of mtDNA-less (ρ0) cells of Mus musculus domesticus with platelets from different species, mtDNA repopulated cybrids were obtained for finding the mtDNA species that could induce mitochondrial abnormalities. Expression of mitochondrial dysfunction might be expected in these cybrids due to incompatibility between nuclear and mitochondrial genomes from different species. The results showed that mouse ρ0 cells could receive mtDNA from a different mouse species, M. spretus, or even mtDNA from the rat, Rattus norvegicus, and that the introduced rat mtDNA, but not M. spretus mtDNA, caused mitochondrial dysfunction, even though rat mtDNA could restore normal mitochondrial translation in the cybrids. Considering that mitochondrial respiratory complexes consist of nuclear DNA- and mtDNA-coded polypeptides, these observations suggest that the nuclear and mitochondrial interactions required for replication, transcription, and translation of introduced rat mtDNA must be less stringently controlled than those required for formation of normal respiratory complexes. As no procedure for introduction of mutagenized mouse mtDNA into living cells has yet been established, these findings provide important insights into generating mtDNA-knockout mice.

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The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation

Nature Communications ◽

10.1038/s41467-021-27905-1 ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Nicole Kleiber ◽

Nicolas Lemus-Diaz ◽

Carina Stiller ◽

Marleen Heinrichs ◽

Mandy Mong-Quyen Mai ◽

...

Keyword(s):

Matrix Protein ◽

Mitochondrial Translation ◽

Stem Loop ◽

Cellular Targets ◽

Trna Recognition ◽

Mitochondrial Ribosomes ◽

Trna Structure ◽

Recognition Elements ◽

And Function

AbstractModified nucleotides in tRNAs are important determinants of folding, structure and function. Here we identify METTL8 as a mitochondrial matrix protein and active RNA methyltransferase responsible for installing m3C32 in the human mitochondrial (mt-)tRNAThr and mt-tRNASer(UCN). METTL8 crosslinks to the anticodon stem loop (ASL) of many mt-tRNAs in cells, raising the question of how methylation target specificity is achieved. Dissection of mt-tRNA recognition elements revealed U34G35 and t6A37/(ms2)i6A37, present concomitantly only in the ASLs of the two substrate mt-tRNAs, as key determinants for METTL8-mediated methylation of C32. Several lines of evidence demonstrate the influence of U34, G35, and the m3C32 and t6A37/(ms2)i6A37 modifications in mt-tRNAThr/Ser(UCN) on the structure of these mt-tRNAs. Although mt-tRNAThr/Ser(UCN) lacking METTL8-mediated m3C32 are efficiently aminoacylated and associate with mitochondrial ribosomes, mitochondrial translation is mildly impaired by lack of METTL8. Together these results define the cellular targets of METTL8 and shed new light on the role of m3C32 within mt-tRNAs.

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The role of mitochondrial DNA in the cancerogenesis of cervix HPV positive women

Annales UMCS Pharmacia ◽

10.2478/v10080-008-0092-z ◽

2008 ◽

Vol 21 (2) ◽

pp. 85-89

Author(s):

Alicja Warowicka ◽

Joanna Pacholska-Bogalska ◽

Anna Kwaśniewska ◽

Anna Goździcka-Józefiak

Keyword(s):

Mitochondrial Dna

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Role of Mitochondrial DNA in Inflammatory Airway Diseases

Comprehensive Physiology ◽

10.1002/cphy.c200010 ◽

2021 ◽

pp. 1485-1499

Author(s):

Ryan J. Snyder ◽

Steven R. Kleeberger

Keyword(s):

Mitochondrial Dna ◽

Airway Diseases

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Advances in the role of miRNAs in the occurrence and development of osteosarcoma

Open Medicine ◽

10.1515/med-2020-0205 ◽

2020 ◽

Vol 15 (1) ◽

pp. 1003-1011

Author(s):

Guanyu Zhang ◽

Yiran Li ◽

Jiasheng Xu ◽

Zhenfang Xiong

Keyword(s):

Target Gene ◽

Early Stage ◽

Research Direction ◽

Research Progress ◽

Skeletal System ◽

Translation Process ◽

Non Coding Rnas ◽

New Research ◽

Post Transcriptional Regulation

AbstractOsteosarcoma (OS) is the most common primary malignant tumor of the skeletal system in the clinic. It mainly occurs in adolescent patients and the pathogenesis of the disease is very complicated. The distant metastasis may occur in the early stage, and the prognosis is poor. MicroRNAs (miRNAs) are non-coding RNAs of about 18–25 nt in length that are involved in post-transcriptional regulation of genes. miRNAs can regulate target gene expression by promoting the degradation of target mRNAs or inhibiting the translation process, thereby the proliferation of OS cells can be inhibited and the apoptosis can be promoted; in this way, miRNAs can affect the metabolism of OS cells and can also participate in the occurrence, invasion, metastasis, and recurrence of OS. Some miRNAs have already been found to be closely related to the prognosis of patients with OS. Unlike other reviews, this review summarizes the miRNA molecules closely related to the development, diagnosis, prognosis, and treatment of OS in recent years. The expression and influence of miRNA molecule on OS were discussed in detail, and the related research progress was summarized to provide a new research direction for early diagnosis and treatment of OS.

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Cytosolic Ribosomal Mutations That Abolish Accumulation of Circular Intron in the Mitochondria Without Preventing Senescence of Podospora anserina

Genetics ◽

10.1093/genetics/145.3.697 ◽

1997 ◽

Vol 145 (3) ◽

pp. 697-705 ◽

Cited By ~ 1

Author(s):

Philippe Silar ◽

France Koll ◽

Michèle Rossignol

Keyword(s):

Mitochondrial Dna ◽

Ribosomal Proteins ◽

Podospora Anserina ◽

Cox1 Gene ◽

Accuracy Control ◽

Additional Function ◽

Mutant Proteins ◽

Double Stranded Dna ◽

Dna Modifications

The filamentous fungus Podospora anserina presents a degeneration syndrome called Senescence associated with mitochondrial DNA modifications. We show that mutations affecting the two different and interacting cytosolic ribosomal proteins (S7 and S19) systematically and specifically prevent the accumulation of senDNAα (a circular double-stranded DNA plasmid derived from the first intron of the mitochondrial cox1 gene or intron α) without abolishing Senescence nor affecting the accumulation of other usually observed mitochondrial DNA rearrangements. One of the mutant proteins is homologous to the Escherichia coli S4 and Saccharomyces cerevisiae S13 ribosomal proteins, known to be involved in accuracy control of cytosolic translation. The lack of accumulation of senDNAα seems to result from a nontrivial ribosomal alteration unrelated to accuracy control, indicating that S7 and S19 proteins have an additional function. The results strongly suggest that modified expression of nucleus-encoded proteins contributes to Senescence in P. anserina. These data do not fit well with some current models, which propose that intron α plays the role of the cytoplasmic and infectious Determinant of Senescence that was defined in early studies.

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Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

Nature Communications ◽

10.1038/s41467-021-23702-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hauke S. Hillen ◽

Elena Lavdovskaia ◽

Franziska Nadler ◽

Elisa Hanitsch ◽

Andreas Linden ◽

...

Keyword(s):

Ribosomal Proteins ◽

Ribosome Biogenesis ◽

Ribosomal Subunit ◽

Structural Basis ◽

Peptidyl Transferase ◽

Mitochondrial Ribosomes ◽

Mitochondrial Ribosome ◽

In Vitro Reconstitution

AbstractRibosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.

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The Role of Mitochondria in Carcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22105100 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5100

Author(s):

Paulina Kozakiewicz ◽

Ludmiła Grzybowska-Szatkowska ◽

Marzanna Ciesielka ◽

Jolanta Rzymowska

Keyword(s):

Prostate Cancer ◽

Mitochondrial Dna ◽

Nuclear Dna ◽

Dna Polymorphisms ◽

Gene Encoding ◽

Dna Mutations ◽

Nadh Ubiquinone Oxidoreductase ◽

Gene Coi ◽

The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

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Functional Characterization of Spliceosomal Introns and Identification of U2, U4, and U5 snRNAs in the Deep-Branching Eukaryote Entamoeba histolytica

Eukaryotic Cell ◽

10.1128/ec.00059-07 ◽

2007 ◽

Vol 6 (6) ◽

pp. 940-948 ◽

Cited By ~ 16

Author(s):

Carrie A. Davis ◽

Michael P. S. Brown ◽

Upinder Singh

Keyword(s):

Entamoeba Histolytica ◽

Splice Site ◽

Expressed Sequence Tag ◽

Functional Characterization ◽

Molecular Evidence ◽

Spliceosomal Introns ◽

Accurate Expression ◽

Eukaryotic Organisms

ABSTRACT Pre-mRNA splicing is essential to ensure accurate expression of many genes in eukaryotic organisms. In Entamoeba histolytica, a deep-branching eukaryote, approximately 30% of the annotated genes are predicted to contain introns; however, the accuracy of these predictions has not been tested. In this study, we mined an expressed sequence tag (EST) library representing 7% of amoebic genes and found evidence supporting splicing of 60% of the testable intron predictions, the majority of which contain a GUUUGU 5′ splice site and a UAG 3′ splice site. Additionally, we identified several splice site misannotations, evidence for the existence of 30 novel introns in previously annotated genes, and identified novel genes through uncovering their spliced ESTs. Finally, we provided molecular evidence for the E. histolytica U2, U4, and U5 snRNAs. These data lay the foundation for further dissection of the role of RNA processing in E. histolytica gene expression.

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