scholarly journals Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes

2021 ◽  
Author(s):  
Iliana C Soto ◽  
Mary Couvillion ◽  
Erik McShane ◽  
Katja G Hansen ◽  
J. Conor Moran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Mitochondrial Dna ◽  
Nuclear Gene ◽  
Cell Types ◽  
Ribosome Profiling ◽  
Nuclear Gene Expression ◽  
Leigh’S Syndrome ◽  
Cellular Compartments ◽  
Translation Systems

Oxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA- encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we established an optimized ribosome profiling approach tailored for the unique features of the human mitoribosome. Analysis of ribosome footprints in five cell types revealed that average mitochondrial synthesis rates corresponded precisely to cytosolic rates across OXPHOS complexes. Balanced mitochondrial and cytosolic synthesis did not rely on rapid feedback between the two translation systems. Rather, LRPPRC, a gene associated with Leigh's syndrome, is required for the reciprocal translatomes and maintains cellular proteostasis. Based on our findings, we propose that human mitonuclear balance is enabled by matching OXPHOS subunit synthesis rates across cellular compartments, which may represent a vulnerability for cellular proteostasis.

scholarly journals HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Manti Guha ◽  
Satish Srinivasan ◽  
Kip Guja ◽  
Edison Mejia ◽  
Miguel Garcia-Diaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Transcriptional Activation ◽  
Nuclear Gene ◽  
C2c12 Cells ◽  
Retrograde Signaling ◽  
Epigenetic Mechanism ◽  
Mitochondrial Stress ◽  
Nuclear Gene Expression ◽  
Mitochondrial Dna Copy Number

Abstract Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced transcription coactivator hnRNAP2 acetylates Lys 8 of H4 through an intrinsic histone lysine acetyltransferase (KAT) activity with Arg 48 and Arg 50 of hnRNAP2 being essential for acetyl-CoA binding and acetyltransferase activity. H4K8 acetylation at the mitochondrial stress-responsive promoters by hnRNAP2 is essential for transcriptional activation. We found that the previously described mitochondria-to-nucleus retrograde signaling-mediated transformation of C2C12 cells caused an increased expression of genes involved in various oncogenic processes, which is retarded in hnRNAP2 silenced or hnRNAP2 KAT mutant cells. Taken together, these data show that altered gene expression by mitochondria-to-nucleus retrograde signaling involves a novel hnRNAP2-dependent epigenetic mechanism that may have a role in cancer and other pathologies.

The cytoskeleton and nucleus: the role of actin as a modulator of neuronal gene expression

e-Neuroforum ◽  
2011 ◽  
Vol 17 (1) ◽  
pp. 1-5 ◽  
Author(s):  
B. Knöll ◽  
H. Beck
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Serum Response Factor ◽  
Nuclear Gene ◽  
Cell Types ◽  
Nuclear Gene Expression ◽  
Cytoskeletal Regulation ◽  
Neuronal Gene ◽  
The Impact ◽  
Serum Response

AbstractActin, arranged for example in stress fibres, provides a fundamental cytoskeletal frame­work function to all cell types. Notably, there is now mounting evidence that, in addition to cytoplasmic cytoskeletal regulation, ac­tin treadmilling provides a signal modulat­ing nuclear gene expression. In altering gene regulation, cytoplasmic and most likely also a nucleus-resident actin provides an addition­al (gene) regulatory twist to cell motility. So far, the transcription factor serum response factor (SRF) alongside its myocardin-relat­ed transcription factor (MRTF) cofactors has emerged as the main target of actin dynam­ics. In this review, we discuss the impact of actin signalling on nuclear gene expression in the nervous system, where the actin-MRTF-SRF module contributes to various processes including neuronal motility.

Differential expression of mRNA in human thyroid cells depleted of mitochondrial DNA by ethidium bromide treatment

1999 ◽  
Vol 97 (2) ◽  
pp. 207-213 ◽  
Author(s):  
A. W. THOMAS ◽  
A. MAJID ◽  
E. J. SHERRATT ◽  
J. W. GAGG ◽  
J. C. ALCOLADO
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Ethidium Bromide ◽  
Nuclear Gene ◽  
Simian Virus 40 ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Mtdna Mutations ◽  
Nuclear Gene Expression

A wide variety of human diseases have been associated with defects in mitochondrial DNA (mtDNA). The exact mechanism by which specific mtDNA mutations cause disease is unknown and, although the disparate phenotypes might be explained on the basis of impaired mitochondrial gene function alone, the role of altered nuclear gene expression must also be considered. In recent years, the experimental technique of depleting cells of mtDNA by culturing them with ethidium bromide has become a popular method of studying mitochondrial disorders. However, apart from depleting mtDNA, ethidium bromide may have many other intracellular and nuclear effects. The aim of the present study was to investigate the effects of ethidium bromide treatment on nuclear gene expression. A simian-virus-40-transformed human thyroid cell line was depleted of mtDNA by culture in ethidium bromide, and differential display reverse transcriptase–PCR (DDRT-PCR) was then employed to compare mRNA expression between wild-type, mtDNA-replete (ρ+) and ethidium bromide-treated, mtDNA-depleted (ρ0) cells. Expression of the majority of nuclear-encoded genes, including those for subunits involved in oxidative phosphorylation, remained unaffected by the treatment. Seven clones were found to be underexpressed; three of the clones showed significant similarity with sequences of the human genes encoding RNase L inhibitor, human tissue factor and ARCN1 (archain vesicle transport protein 1), a highly conserved species which is related to vesicle structure and trafficking proteins. We conclude that the effects of ethidium bromide treatment on nuclear gene expression are not simply limited to changes in pathways directly associated with known mitochondrial function. Further studies will be required to elucidate which of these changes are due to mtDNA depletion, ATP deficiency or other disparate effects of ethidium bromide exposure. Given that most genes appear unaffected, the results suggest that depleting cells of mtDNA by ethidium bromide treatment is a valuable approach for the study of mitochondrial mutations by cybrid techniques.

Chloroplast Redox Control of Nuclear Gene Expression—A New Class of Plastid Signals in Interorganellar Communication

2003 ◽  
Vol 5 (1) ◽  
pp. 95-101 ◽  
Author(s):  
Thomas Pfannschmidt ◽  
Katia Schütze ◽  
Vidal Fey ◽  
Irena Sherameti ◽  
Ralf Oelmüller
Keyword(s):  
Gene Expression ◽  
Nuclear Gene ◽  
Redox Control ◽  
New Class ◽  
Nuclear Gene Expression

scholarly journals Introns mediate post-transcriptional enhancement of nuclear gene expression in the green microalga Chlamydomonas reinhardtii

PLoS Genetics ◽  
2020 ◽  
Vol 16 (7) ◽  
pp. e1008944 ◽  
Author(s):  
Thomas Baier ◽  
Nick Jacobebbinghaus ◽  
Alexander Einhaus ◽  
Kyle J. Lauersen ◽  
Olaf Kruse
Keyword(s):  
Gene Expression ◽  
Chlamydomonas Reinhardtii ◽  
Nuclear Gene ◽  
Nuclear Gene Expression ◽  
Green Microalga

scholarly journals Dinoflagellate Host Chloroplasts and Mitochondria Remain Functional During Amoebophrya Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Ehsan Kayal ◽  
Catharina Alves-de-Souza ◽  
Sarah Farhat ◽  
Lourdes Velo-Suarez ◽  
Joanne Monjol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Carbon Fixation ◽  
Nuclear Gene ◽  
Host Cells ◽  
Infection Period ◽  
Nuclear Gene Expression ◽  
Intracellular Parasites ◽  
Electron Transport Chains ◽  
Complete Digestion ◽  
Host Nucleus

Dinoflagellates are major components of phytoplankton that play critical roles in many microbial food webs, many of them being hosts of countless intracellular parasites. The phototrophic dinoflagellate Scrippsiella acuminata (Dinophyceae) can be infected by the microeukaryotic parasitoids Amoebophrya spp. (Syndiniales), some of which primarily target and digest the host nucleus. Early digestion of the nucleus at the beginning of the infection is expected to greatly impact the host metabolism, inducing the knockout of the organellar machineries that highly depend upon nuclear gene expression, such as the mitochondrial OXPHOS pathway and the plastid photosynthetic carbon fixation. However, previous studies have reported that chloroplasts remain functional in swimming host cells infected by Amoebophrya. We report here a multi-approach monitoring study of S. acuminata organelles over a complete infection cycle by nucleus-targeting Amoebophrya sp. strain A120. Our results show sustained and efficient photosystem II activity as a hallmark of functional chloroplast throughout the infection period despite the complete digestion of the host nucleus. We also report the importance played by light on parasite production, i.e., the amount of host biomass converted to parasite infective propagules. Using a differential gene expression analysis, we observed an apparent increase of all 3 mitochondrial and 9 out of the 11 plastidial genes involved in the electron transport chains (ETC) of the respiration pathways during the first stages of the infection. The longer resilience of organellar genes compared to those encoded by the nucleus suggests that both mitochondria and chloroplasts remain functional throughout most of the infection. This extended organelle functionality, along with higher parasite production under light conditions, suggests that host bioenergetic organelles likely benefit the parasite Amoebophrya sp. A120 and improve its fitness during the intracellular infective stage.

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