Translation termination in human mitochondria – substrate specificity of mitochondrial release factors DOI Creative Commons

Franziska Nadler,

Ricarda Richter‐Dennerlein

Biological Chemistry, Год журнала: 2023, Номер 404(8-9), С. 769 - 779

Опубликована: Июнь 28, 2023

Mitochondria are the essential players in eukaryotic ATP production by oxidative phosphorylation, which relies on maintenance and accurate expression of mitochondrial genome. Even though basic principles translation conserved due to descendance from a bacterial ancestor, some deviations regarding factors as well mRNA characteristics applied genetic code present human mitochondria. Together, these features certain challenges during mitochondrion has handle. Here, we discuss current knowledge focusing termination process associated quality control mechanisms. We describe how mtRF1a resembles RF1 mechanistically summarize vitro recent vivo data leading conclusion being major release factor. On other hand, ongoing debate about function second codon-dependent factor mtRF1 its role specialized Finally, link defects activation rescue mechanisms highlighting importance ribosome-associated for sufficient respiratory therefore health.

Язык: Английский

Organization and expression of the mammalian mitochondrial genome DOI
Oliver Rackham, Aleksandra Filipovska

Nature Reviews Genetics, Год журнала: 2022, Номер 23(10), С. 606 - 623

Опубликована: Апрель 22, 2022

Язык: Английский

Процитировано

98

A kinetic dichotomy between mitochondrial and nuclear gene expression processes DOI
Erik McShane, Mary Couvillion, Robert Ietswaart

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(8), С. 1541 - 1555.e11

Опубликована: Март 18, 2024

Язык: Английский

Процитировано

25

Mechanisms and regulation of human mitochondrial transcription DOI
Benedict G. Tan, Claes M. Gustafsson, Maria Falkenberg

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 25(2), С. 119 - 132

Опубликована: Окт. 2, 2023

Язык: Английский

Процитировано

43

The human mitochondrial mRNA structurome reveals mechanisms of gene expression DOI
J. Conor Moran, Amir Brivanlou, Michele Brischigliaro

и другие.

Science, Год журнала: 2024, Номер 385(6706)

Опубликована: Июль 18, 2024

The human mitochondrial genome encodes crucial oxidative phosphorylation system proteins, pivotal for aerobic energy transduction. They are translated from nine monocistronic and two bicistronic transcripts whose native structures remain unexplored, posing a gap in understanding gene expression. In this work, we devised the dimethyl sulfate mutational profiling with sequencing (mitoDMS-MaPseq) method applied detection of RNA folding ensembles using expectation-maximization (DREEM) clustering to unravel messenger (mt-mRNA) structurome wild-type (WT) leucine-rich pentatricopeptide repeat-containing protein (LRPPRC)-deficient cells. Our findings elucidate LRPPRC's role as holdase contributing maintaining mt-mRNA efficient translation. structural insights WT mitochondria, coupled metabolic labeling, unveil potential mRNA-programmed translational pausing distinct programmed ribosomal frameshifting mechanism. data define critical layer expression regulation. These maps provide reference studying diverse physiological pathological contexts.

Язык: Английский

Процитировано

9

Advances in human pre-tRNA maturation : TRMT10C and ELAC2 in focus DOI Creative Commons

Juhi Sikarwar,

Vincent Meynier, Carine Tisné

и другие.

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 168989 - 168989

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1

Metal Complexes in Target-Specific Anticancer Therapy: Recent Trends and Challenges DOI Creative Commons
Gemechu Shumi, Tegene Desalegn, Taye B. Demissie

и другие.

Journal of Chemistry, Год журнала: 2022, Номер 2022, С. 1 - 19

Опубликована: Май 17, 2022

Cancer is characterized by abnormal cell differentiation in or on the part of body. The most commonly used chemotherapeutic drugs are developed to target rapidly dividing cells, such as cancer but they also damage healthy epithelial cells. This has serious consequences for normal cells and become responsible development various disorders. Several strategies delivering cytotoxic cancerous sites that limit systemic toxicity other adverse effects have recently been evolved. Among them, biomolecule-conjugated metal complexes-based targeting shown tremendous advantages therapy. review focuses several chemoselective biomolecules-bound complexes prospective therapy-targeted agents. In this review, we presented details extra- intracellular mechanisms We addressed current clinical issues recent therapeutic targeted therapy may pave a way future direction

Язык: Английский

Процитировано

36

The human mitochondrial genome contains a second light strand promoter DOI Creative Commons
Benedict G. Tan, Christian D. Mutti, Yonghong Shi

и другие.

Molecular Cell, Год журнала: 2022, Номер 82(19), С. 3646 - 3660.e9

Опубликована: Авг. 30, 2022

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism supply cells with adequate levels of adenosine triphosphate. Central this process is the idea that replication primers gene products both arise via transcription from single light strand promoter (LSP) such primer formation can influence expression, no consensus as how regulated. Here, we report discovery second (LSP2) humans, features characteristic bona fide promoter. We propose position LSP2 on allows expression orchestrated two distinct sites, which expands our long-held understanding humans.

Язык: Английский

Процитировано

36

Mitochondrial DNA quality control in the female germline requires a unique programmed mitophagy DOI Creative Commons

Jonathan M. Palozzi,

Swathi P. Jeedigunta,

Anastasia V. Minenkova

и другие.

Cell Metabolism, Год журнала: 2022, Номер 34(11), С. 1809 - 1823.e6

Опубликована: Ноя. 1, 2022

Язык: Английский

Процитировано

29

High expression of novel biomarker TBRG4 promotes the progression and invasion of oral squamous cell carcinoma DOI

Abilasha Ramasubramanian,

Pratibha Ramani, Balachander Kannan

и другие.

Journal of Oral Pathology and Medicine, Год журнала: 2023, Номер 52(8), С. 738 - 745

Опубликована: Авг. 3, 2023

Abstract Background Transforming growth factor β regulator 4 (TBRG4) is a potential prognostic indicator in various cancers, especially squamous cell carcinomas, and associated with disease amelioration poor outcomes. The study aimed to assess the expression pattern of TBRG4 patients operable oral carcinoma (OSCC) understand its role tumour progression using indicators outcome like stage, grade, nodal metastasis, invasion. Methods was assessed by analyzing 51 cancer adjacent non‐cancerous tissues OSCC quantitative real‐time PCR, Western blot. also analysed Cancer Genome Atlas Head–Neck Squamous Cell Carcinoma (TCGA‐HNSC) dataset UALCAN tool ( http://ualcan.path.uab.edu/ ). relationship between patient's prognosis Kaplan–Meier plotter. Results Both mRNA protein levels were significantly increased tissues. TBGR4 advanced stages (III IV) worst invasion (WPOI‐4 5). High reduced overall survival p = 0.011). In addition, analysis gene clinical data from TCGA, identified that highly expressed HPV negative positively correlated survival. Conclusion present suggests high might serve as novel biomarker for HPV‐negative OSCC, which can be validated future additional investigations larger cohorts along functional studies.

Язык: Английский

Процитировано

14

The molecular machinery for maturation of primary mtDNA transcripts DOI Creative Commons
Ana Vučković, Christoph Freyer, Anna Wredenberg

и другие.

Human Molecular Genetics, Год журнала: 2024, Номер 33(R1), С. R19 - R25

Опубликована: Май 22, 2024

Human mitochondria harbour a circular, polyploid genome (mtDNA) encoding 11 messenger RNAs (mRNAs), two ribosomal (rRNAs) and 22 transfer (tRNAs). Mitochondrial transcription produces long, polycistronic transcripts that span almost the entire length of genome, hence contain all three types RNAs. The primary then undergo number processing maturation steps, which constitute key regulatory points mitochondrial gene expression. first step RNA consists separation into individual, functional molecules can occur by distinct pathways. Both are carried out dedicated molecular machineries substantially differ from enzymes found elsewhere. As result, underlying mechanisms remain poorly understood. Over last years, genetic, biochemical structural studies have identified players involved in both pathways provided insights mechanisms. Here, we review our current understanding mammalian provide an outlook on open questions field.

Язык: Английский

Процитировано

5