scholarly journals MRX8, the conserved mitochondrial YihA GTPase family member is required for de novo Cox1 synthesis at suboptimal temperatures in Saccharomyces cerevisiae

2021 ◽  
pp. mbc.E20-07-0457
Author(s):  
Yash Verma ◽  
Upasana Mehra ◽  
Dharmendra Kumar Pandey ◽  
Joy Kar ◽  
Xochitl Pérez-Martinez ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
De Novo ◽  
Mitochondrial Protein ◽  
Cellular Respiration ◽  
Catalytic Core ◽  
Mitochondrial Ribosomes ◽  
Oxphos System ◽  
Guanine Nucleotide Binding ◽  
Human Orthologue

The synthesis of Cox1, the conserved catalytic-core subunit of Complex IV, a multi-subunit machinery of the mitochondrial oxidative phosphorylation (OXPHOS) system under environmental stress is not sufficiently addressed. In this study, we show that the putative YihA superfamily GTPase, Mrx8 is a bonafide mitochondrial protein required for Cox1 translation initiation and elongation during suboptimal growth condition at 16°C. Mrx8 was found in a complex with mitochondrial ribosomes, consistent with a role in protein synthesis. Cells expressing mutant Mrx8 predicted to be defective in guanine nucleotide binding and hydrolysis were compromised for robust cellular respiration. We show that requirement of Pet309 and Mss51 for cellular respiration is not bypassed by overexpression of Mrx8 and vice versa. Consistently the ribosomal association of Mss51 is independent of Mrx8. Significantly, we find that GTPBP8, the human orthologue, complements the loss of cellular respiration in Δmrx8 cells and GTPBP8 localizes to the mitochondria in mammalian cells. This strongly suggest a universal role of MRX8 family of proteins in regulating mitochondrial function.

scholarly journals A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mammalian Cells ◽  
De Novo ◽  
Adenosine Monophosphate ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

scholarly journals DNA Demethylation Pathways: Recent Insights

2013 ◽  
Vol 5 ◽  
pp. GEG.S12143 ◽  
Author(s):  
Cong-jun Li
Keyword(s):  
Dna Methylation ◽  
Mammalian Cells ◽  
De Novo ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Sequencing Technologies ◽  
Active Dna Demethylation ◽  
Mammalian Genomes ◽  
Genome Context

DNA methylation is a major epigenetic regulatory mechanism for gene expression and cell differentiation. Until recently, it was still unclear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether or not active demethylating activity is involved. Even the role of molecules and the mechanisms underlying the processes of active demethylation itself is blurred. Emerging sequencing technologies have led to recent insights into the dynamic distribution of DNA methylation during development and the role of this epigenetic mark within a distinct genome context, such as the promoters, exons, or imprinted control regions. This review summarizes recent insights on the dynamic nature of DNA methylation and demethylation, as well as the mechanisms regulating active DNA demethylation in mammalian cells, which have been fundamental research interests in the field of epigenomics.

scholarly journals Protein Interaction Patterns in Arabidopsis thaliana Leaf Mitochondria Change in Response to Illumination

2020 ◽  
Author(s):  
Nils Rugen ◽  
Frank Schaarschmidt ◽  
Hans-Peter Braun ◽  
Holger Eubel
Keyword(s):  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Tca Cycle ◽  
Mass Range ◽  
Cellular Respiration ◽  
Interaction Patterns ◽  
Large Protein ◽  
The Tca Cycle ◽  
Mitochondrial Functions

Mitochondrial biology is underpinned by the presence and activity of large protein complexes participating in the organelle-located parts of cellular respiration, the TCA cycle and oxidative phosphorylation. While the enzymatic roles of these complexes are undisputed, little is known about the interactions of the subunits beyond their presence in the monomeric protein complexes and their functions in regulating mitochondria metabolism. By applying one of the most important regulatory cues for plant metabolism, the presence or absence of light, we here assess the changes in the composition and molecular mass of known mitochondrial protein complexes by employing a differential complexome profiling strategy. Covering a mass range up to 25 MDa, we demonstrate dynamic associations of TCA-cycle enzymes and of OXPHOS components. The data presented here form the basis for future studies aiming to advance our understanding of the role of protein:protein interactions in the regulation of plant mitochondrial functions.

9 A NOVEL ROLE OF SPHINGOSINE KINASE 1 IN THE DE NOVO BIOSYNTHESIS OF DIHYDROSPHINGOSINE-1-PHOSPHATE IN MAMMALIAN CELLS.

2006 ◽  
Vol 54 (2) ◽  
pp. S345.3-S345
Author(s):  
E. Berdyshev ◽  
I. Gorshkova ◽  
P. Usatyuk ◽  
Y. Zhao ◽  
B. Saatian ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
De Novo ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
De Novo Biosynthesis

scholarly journals Mitochondrial NAD-Dependent Methylenetetrahydrofolate Dehydrogenase-Methenyltetrahydrofolate Cyclohydrolase Is Essential for Embryonic Development

2002 ◽  
Vol 22 (12) ◽  
pp. 4158-4166 ◽  
Author(s):  
E. Di Pietro ◽  
J. Sirois ◽  
M. L. Tremblay ◽  
R. E. MacKenzie
Keyword(s):  
Protein Synthesis ◽  
Embryonic Development ◽  
Mammalian Cells ◽  
Mutant Cell ◽  
Mitochondrial Protein ◽  
Wild Type ◽  
Mitochondrial Translation ◽  
Metabolic Role ◽  
Methylenetetrahydrofolate Dehydrogenase

ABSTRACT Folate-dependent enzymes are compartmentalized between the cytoplasm and mitochondria of eukaryotes. The role of mitochondrial folate-dependent metabolism and the extent of its contribution to cytoplasmic processes are areas of active investigation. NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) catalyzes the interconversion of 5,10-methylenetetrahydrofolate and 10-formyltetrahydrofolate in mitochondria of mammalian cells, but its metabolic role is not yet clear. Its expression in embryonic tissues but not in most adult tissues as well as its stringent transcriptional regulation led us to postulate that it may play a role in embryonic development. To investigate the metabolic role of NMDMC, we used a knockout approach to delete the nmdmc gene in mice. Heterozygous mice appear healthy, but homozygous NMDMC knockout mice die in utero. At embryonic day 12.5 (E12.5), homozygous null embryos exhibit no obvious developmental defects but are smaller and pale and die soon thereafter. Mutant fetal livers contain fewer nucleated cells and lack the characteristic redness of wild-type or heterozygous livers. The frequencies of CFU-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) from fetal livers of E12.5 null mutants were not reduced compared with those of wild-type or heterozygous embryos. It has been assumed that initiation of protein synthesis in mitochondria requires a formylated methionyl-tRNAfmet. One role postulated for NMDMC is to provide 10-formyltetrahydrofolate as a formyl group donor for the synthesis of this formylmethionyl-tRNAfmet. To determine if the loss of NMDMC impairs protein synthesis and thus could be a cause of embryonic lethality, mitochondrial translation products were examined in cells in culture. Mitochondrial protein synthesis was unaffected in NMDMC-null mutant cell lines compared with the wild type. These results show that NMDMC is not required to support initiation of protein synthesis in mitochondria in isolated cells but instead demonstrate an essential role for mitochondrial folate metabolism during embryonic development.

scholarly journals The Mitochondrial Protein hFis1 Regulates Mitochondrial Fission in Mammalian Cells through an Interaction with the Dynamin-Like Protein DLP1

2003 ◽  
Vol 23 (15) ◽  
pp. 5409-5420 ◽  
Author(s):  
Yisang Yoon ◽  
Eugene W. Krueger ◽  
Barbara J. Oswald ◽  
Mark A. McNiven
Keyword(s):  
Mammalian Cells ◽  
Mitochondrial Fission ◽  
Mitochondrial Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Limiting Factor ◽  
Mitochondrial Morphology ◽  
Mammalian Homologue ◽  
Terminal Structure

ABSTRACT The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p. In mammalian cells, the dynamin-like protein DLP1/Drp1 functions as a mitochondrial fission protein, but the mechanisms by which DLP1/Drp1 and the mitochondrial membrane interact during the fission process are undefined. In this study, we have tested the role of a mammalian homologue of Fis1p, hFis1, and provided new and mechanistic information about the control of mitochondrial fission in mammalian cells. Through differential tagging and deletion experiments, we demonstrate that the intact C-terminal structure of hFis1 is essential for mitochondrial localization, whereas the N-terminal region of hFis1 is necessary for mitochondrial fission. Remarkably, an increased level of cellular hFis1 strongly promotes mitochondrial fission, resulting in an accumulation of fragmented mitochondria. Conversely, cell microinjection of hFis1 antibodies or treatment with hFis1 antisense oligonucleotides induces an elongated and collapsed mitochondrial morphology. Further, fluorescence resonance energy transfer and coimmunoprecipitation studies demonstrate that hFis1 interacts with DLP1. These results suggest that hFis1 participates in mitochondrial fission through an interaction that recruits DLP1 from the cytosol. We propose that hFis1 is a limiting factor in mitochondrial fission and that the number of hFis1 molecules on the mitochondrial surface determines fission frequency.

scholarly journals A Novel Role of Sphingosine Kinase 1 in the de novo Biosynthesis of Dihydrosphingosine‐1‐Phosphate in Mammalian Cells.

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
E. Berdyshev ◽  
I. Gorshkova ◽  
P. Usatyuk ◽  
Y. Zhao ◽  
B. Saatian ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
De Novo ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
De Novo Biosynthesis

scholarly journals The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells

Biochimie ◽  
2017 ◽  
Vol 138 ◽  
pp. 156-167 ◽  
Author(s):  
Stanley M.H. Chan ◽  
Xuechan Zhao ◽  
Abdulsalam Elfowiris ◽  
Cherubina Ratnam ◽  
Terence P. Herbert
Keyword(s):  
Protein Synthesis ◽  
Er Stress ◽  
Mrna Expression ◽  
Mammalian Cells ◽  
De Novo ◽  
De Novo Protein Synthesis ◽  
Expression In Mammalian Cells

scholarly journals Identification of Palmitoleic Acid Controlled by mTOR Signaling as a Biomarker of Polymyositis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Geng Yin ◽  
Ying Wang ◽  
Xiao-min Cen ◽  
Yuan Yang ◽  
Min Yang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Palmitoleic Acid ◽  
Mononuclear Cells ◽  
De Novo ◽  
Mtor Signaling ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Reactions ◽  
Mechanistic Target Of Rapamycin ◽  
Novel Biomarkers

Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactionsvialipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC) as a biomarker of polymyositis and offers new targets to the clinical therapy.

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

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