scholarly journals On Message Ribonucleic Acids Targeting to Mitochondria

2009 ◽  
Vol 2 ◽  
pp. BCI.S3745 ◽  
Author(s):  
Di Ding ◽  
Kunjan R. Dave ◽  
Sanjoy K. Bhattacharya

Mitochondria are subcellular organelles that provide energy for a variety of basic cellular processes in eukaryotic cells. Mitochondria maintain their own genomes and many of their endosymbiont genes are encoded by nuclear genomes. The crosstalk between the mitochondrial and nuclear genomes ensures mitochondrial biogenesis, dynamics and maintenance. Mitochondrial proteins are partly encoded by nucleus and synthesized in the cytosol and partly in the mitochondria coded by mitochondrial genome. The efficiency of transport systems that transport nuclear encoded gene products such as proteins and mRNAs to the mitochondrial vicinity to allow for their translation and/or import are recently receiving wide attention. There is currently no concrete evidence that nuclear encoded mRNA is transported into the mitochondria, however, they can be transported onto the mitochondrial surface and translated at the surface of mitochondria utilizing cytosolic machinery. In this review we present an overview of the recent advances in the mRNA transport, with emphasis on the transport of nuclear-encoded mitochondrial protein mRNA into the mitochondria.

2021 ◽  
Author(s):  
Barbara Uszczynska-Ratajczak ◽  
Sreedevi Sugunan ◽  
Monika Kwiatkowska ◽  
Maciej Migdal ◽  
Silvia Carbonell-Sala ◽  
...  

Most mitochondrial proteins are encoded by nuclear genes, synthetized in the cytosol and targeted into the organelle. The import of some, but not all, nuclear-encoded mitochondrial proteins begins with translation of messenger RNAs (mRNAs) on the surface of mitochondria. To characterize the spatial organization of mitochondrial gene products in zebrafish (Danio rerio), we sequenced RNA from different cellular fractions. Our results confirmed the presence of nuclear-encoded mRNAs in the mitochondrial fraction, which in unperturbed conditions, are mainly transcripts encoding large proteins with specific properties, like transmembrane domains. To further explore the principles of mitochondrial protein compartmentalization in zebrafish, we quantified the transcriptomic changes for each subcellular fraction triggered by the chchd4a-/- mutation, causing the disorders in the mitochondrial protein import. Our results indicate that the proteostatic stress further restricts the population of transcripts on the mitochondrial surface, allowing only the largest and the most evolutionary conserved proteins to be synthetized there. We also show that many nuclear-encoded mitochondrial transcripts translated by the cytosolic ribosomes stay resistant to the global translation shutdown. Thus, vertebrates, in contrast to yeast, are not likely to employ localized translation to facilitate synthesis of mitochondrial proteins under proteostatic stress conditions.


2018 ◽  
Vol 46 (5) ◽  
pp. 1225-1238 ◽  
Author(s):  
Thomas Daniel Jackson ◽  
Catherine Sarah Palmer ◽  
Diana Stojanovski

Mitochondria are essential organelles which perform complex and varied functions within eukaryotic cells. Maintenance of mitochondrial health and functionality is thus a key cellular priority and relies on the organelle's extensive proteome. The mitochondrial proteome is largely encoded by nuclear genes, and mitochondrial proteins must be sorted to the correct mitochondrial sub-compartment post-translationally. This essential process is carried out by multimeric and dynamic translocation and sorting machineries, which can be found in all four mitochondrial compartments. Interestingly, advances in the diagnosis of genetic disease have revealed that mutations in various components of the human import machinery can cause mitochondrial disease, a heterogenous and often severe collection of disorders associated with energy generation defects and a multisystem presentation often affecting the cardiovascular and nervous systems. Here, we review our current understanding of mitochondrial protein import systems in human cells and the molecular basis of mitochondrial diseases caused by defects in these pathways.


2021 ◽  
Author(s):  
Hong Xu

The social amoeba Dictyostelium discoideum is a well-established model to study numerous cellular processes including cell motility, chemotaxis, and differentiation. As energy metabolism is involved in these processes, mitochondrial genetics and bioenergetics are of interest, though many features of Dictyostelium mitochondria differ from metazoans. A comprehensive inventory of mitochondrial proteins is critical to understanding mitochondrial processes and their involvement in various cellular pathways. Here, we utilized high-throughput multiplexed protein quantitation and homology analyses to generate a high-confidence mitochondrial protein compendium. Our proteomic approach, which utilizes quantitative mass spectrometry in combination with mathematical modeling, was validated through mitochondrial targeting sequence prediction and live-cell imaging. Our final compendium consists of 1082 proteins. Within our D. discoideum mitochondrial proteome, we identify many proteins that are not present in humans, yeasts, or the ancestral alpha-proteobacteria, which can serve as a foundation for future investigations into the unique mitochondria of Dictyostelium. Additionally, we leverage our compendium to highlight the complexity of metabolic reprogramming during starvation-induced development. Our compendium lays a foundation to investigate mitochondrial processes that are unique in protists, as well as for future studies to understand the functions of conserved mitochondrial proteins in health and diseases using D. discoideum as the model.


Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 173
Author(s):  
Panagiotis Karakaidos ◽  
Theodoros Rampias

In eukaryotic cells, mitochondria originated in an α-proteobacterial endosymbiont. Although these organelles harbor their own genome, the large majority of genes, originally encoded in the endosymbiont, were either lost or transferred to the nucleus. As a consequence, mitochondria have become semi-autonomous and most of their processes require the import of nuclear-encoded components to be functional. Therefore, the mitochondrial-specific translation has evolved to be coordinated by mitonuclear interactions to respond to the energetic demands of the cell, acquiring unique and mosaic features. However, mitochondrial-DNA-encoded genes are essential for the assembly of the respiratory chain complexes. Impaired mitochondrial function due to oxidative damage and mutations has been associated with numerous human pathologies, the aging process, and cancer. In this review, we highlight the unique features of mitochondrial protein synthesis and provide a comprehensive insight into the mitonuclear crosstalk and its co-evolution, as well as the vulnerabilities of the animal mitochondrial genome.


2021 ◽  
Author(s):  
Anna V Freitas ◽  
Jake T Herb ◽  
Miao Pan ◽  
Yong Cheng ◽  
Marjan Gucek ◽  
...  

Abstract The social amoeba Dictyostelium discoideum is a well-established model to study numerous cellular processes including cell motility, chemotaxis, and differentiation. As energy metabolism is involved in these processes, mitochondrial genetics and bioenergetics are of interest, though many features of Dictyostelium mitochondria differ from metazoans. A comprehensive inventory of mitochondrial proteins is critical to understanding mitochondrial processes and their involvement in various cellular pathways. Here, we utilized high-throughput multiplexed protein quantitation and homology analyses to generate a high-confidence mitochondrial protein compendium. Our proteomic approach, which utilizes quantitative mass spectrometry in combination with mathematical modeling, was validated through mitochondrial targeting sequence prediction and live-cell imaging. Our final compendium consists of 1082 proteins. Within our D. discoideum mitochondrial proteome, we identify many proteins that are not present in humans, yeasts, or the ancestral alpha-proteobacteria, which can serve as a foundation for future investigations into the unique mitochondria of Dictyostelium. Additionally, we leverage our compendium to highlight the complexity of metabolic reprogramming during starvation-induced development. Our compendium lays a foundation to investigate mitochondrial processes that are unique in protists, as well as for future studies to understand the functions of conserved mitochondrial proteins in health and diseases using D. discoideum as the model.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andreia I. Pimenta ◽  
Nuno Bernardes ◽  
Marta M. Alves ◽  
Dalila Mil-Homens ◽  
Arsenio M. Fialho

AbstractBurkholderia cenocepacia is known for its capacity of adherence and interaction with the host, causing severe opportunistic lung infections in cystic fibrosis patients. In this work we produced Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line and validated their use as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia. RNA-sequencing was performed and the analysis of the B. cenocepacia K56-2 transcriptome after the first contacts with the surface of host cells allowed the recognition of genes implicated in bacterial adaptation and virulence-associated functions. The sensing of host membranes led to a transcriptional shift that caused a cascade of metabolic and physiological adaptations to the host specific environment. Many of the differentially expressed genes encode proteins related with central metabolic pathways, transport systems, cellular processes, and virulence traits. The understanding of the changes in gene expression that occur in the early steps of infection can uncover new proteins implicated in B. cenocepacia-host cell adhesion, against which new blocking agents could be designed to control the progression of the infectious process.


2021 ◽  
Vol 22 (16) ◽  
pp. 8427
Author(s):  
Beata Smolarz ◽  
Anna Zadrożna-Nowak ◽  
Hanna Romanowicz

Long noncoding RNAs (lncRNAs) are the largest groups of ribonucleic acids, but, despite the increasing amount of literature data, the least understood. Given the involvement of lncRNA in basic cellular processes, especially in the regulation of transcription, the role of these noncoding molecules seems to be of great importance for the proper functioning of the organism. Studies have shown a relationship between disturbed lncRNA expression and the pathogenesis of many diseases, including cancer. The present article presents a detailed review of the latest reports and data regarding the importance of lncRNA in the development of cancers, including breast carcinoma.


BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 390-393
Author(s):  
F.-Nora Vögtle

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.


2020 ◽  
Vol 22 (1) ◽  
pp. 1
Author(s):  
Alessandra Ferramosca

Mitochondria are double membrane-bound organelles which are essential for the viability of eukaryotic cells, because they play a crucial role in bioenergetics, metabolism and signaling [...]


Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.


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