scholarly journals Mitochondrial proteome of mouse oocytes and cisplatin-induced shifts in protein profile

2021 ◽  
Author(s):  
Na Zhang ◽  
An-di Sun ◽  
Si-man Sun ◽  
Rui Yang ◽  
Yan-yan Shi ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Protein Profile ◽  
Chemotherapeutic Agents ◽  
Mitochondrial Proteins ◽  
Cellular Respiration ◽  
Inherited Disorders ◽  
Mitochondrial Proteome ◽  
Mouse Oocytes ◽  
Atp Metabolism ◽  
Functional Components

AbstractMitochondria are essential organelles that provide energy for mammalian cells and participate in multiple functions, such as signal transduction, cellular differentiation, and regulation of apoptosis. Compared with the mitochondria in somatic cells, oocyte mitochondria have an additional level of importance since they are required for germ cell maturation, dysfunction in which can lead to severe inherited disorders. Thus, a systematic proteomic profile of oocyte mitochondria is urgently needed to support the basic and clinical research, but the acquisition of such a profile has been hindered by the rarity of oocyte samples and technical challenges associated with capturing mitochondrial proteins from live oocytes. Here, in this work, using proximity labeling proteomics, we established a mitochondria-specific ascorbate peroxidase (APEX2) reaction in live GV-stage mouse oocytes and identified a total of 158 proteins in oocyte mitochondria. This proteome includes intrinsic mitochondrial structural and functional components involved in processes associated with “cellular respiration”, “ATP metabolism”, “mitochondrial transport”, etc. In addition, mitochondrial proteome capture after oocyte exposure to the antitumor chemotherapeutic cisplatin revealed differential changes in the abundance of several oocyte-specific mitochondrial proteins. Our study provides the first description of a mammalian oocyte mitochondrial proteome of which we are aware, and further illustrates the dynamic shifts in protein abundance associated with chemotherapeutic agents.

scholarly journals The Dual Origin of the Yeast Mitochondrial Proteome

Yeast ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 170-187 ◽  
Author(s):  
Olof Karlberg ◽  
Björn Canbäck ◽  
Charles G. Kurland ◽  
Siv G. E. Andersson
Keyword(s):  
Nuclear Genome ◽  
Mitochondrial Proteins ◽  
Mitochondrial Proteome ◽  
Phylogenetic Reconstructions ◽  
Eukaryotic Genes ◽  
Genes Encoding ◽  
Parallel Mode ◽  
Bacterial Genes ◽  
Dual Origin ◽  
Regulatory Functions

We propose a scheme for the origin of mitochondria based on phylogenetic reconstructions with more than 400 yeast nuclear genes that encode mitochondrial proteins. Half of the yeast mitochondrial proteins have no discernable bacterial homologues, while one-tenth are unequivocally of α-proteobacterial origin. These data suggest that the majority of genes encoding yeast mitochondrial proteins are descendants of two different genomic lineages that have evolved in different modes. First, the ancestral free-living α-proteobacterium evolved into an endosymbiont of an anaerobic host. Most of the ancestral bacterial genes were lost, but a small fraction of genes supporting bioenergetic and translational processes were retained and eventually transferred to what became the host nuclear genome. In a second, parallel mode, a larger number of novel mitochondrial genes were recruited from the nuclear genome to complement the remaining genes from the bacterial ancestor. These eukaryotic genes, which are primarily involved in transport and regulatory functions, transformed the endosymbiont into an ATP-exporting organelle.

Strangers in strange lands: mitochondrial proteins found at extra-mitochondrial locations

2019 ◽  
Vol 476 (1) ◽  
pp. 25-37 ◽  
Author(s):  
David P. Scanlon ◽  
Michael W. Salter
Keyword(s):  
Mitochondrial Genome ◽  
Mitochondrial Function ◽  
Mitochondrial Proteins ◽  
Dual Citizenship ◽  
Mitochondrial Proteome ◽  
Encoded Proteins

Abstract The mitochondrial proteome is estimated to contain ∼1100 proteins, the vast majority of which are nuclear-encoded, with only 13 proteins encoded by the mitochondrial genome. The import of these nuclear-encoded proteins into mitochondria was widely believed to be unidirectional, but recent discoveries have revealed that many these ‘mitochondrial’ proteins are exported, and have extra-mitochondrial activities divergent from their mitochondrial function. Surprisingly, three of the exported proteins discovered thus far are mitochondrially encoded and have significantly different extra-mitochondrial roles than those performed within the mitochondrion. In this review, we will detail the wide variety of proteins once thought to only reside within mitochondria, but now known to ‘emigrate’ from mitochondria in order to attain ‘dual citizenship’, present both within mitochondria and elsewhere.

scholarly journals Mosaic nature of the mitochondrial proteome: Implications for the origin and evolution of mitochondria

2015 ◽  
Vol 112 (33) ◽  
pp. 10133-10138 ◽  
Author(s):  
Michael W. Gray
Keyword(s):  
Phylogenetic Signal ◽  
Phylogenetic Analyses ◽  
Large Fraction ◽  
Mitochondrial Proteins ◽  
Surprising Result ◽  
Origin And Evolution ◽  
Mitochondrial Proteome ◽  
Mitochondrial Origin ◽  
Conserved Core ◽  
Evolution Of Mitochondria

Comparative studies of the mitochondrial proteome have identified a conserved core of proteins descended from the α-proteobacterial endosymbiont that gave rise to the mitochondrion and was the source of the mitochondrial genome in contemporary eukaryotes. A surprising result of phylogenetic analyses is the relatively small proportion (10–20%) of the mitochondrial proteome displaying a clear α-proteobacterial ancestry. A large fraction of mitochondrial proteins typically has detectable homologs only in other eukaryotes and is presumed to represent proteins that emerged specifically within eukaryotes. A further significant fraction of the mitochondrial proteome consists of proteins with homologs in prokaryotes, but without a robust phylogenetic signal affiliating them with specific prokaryotic lineages. The presumptive evolutionary source of these proteins is quite different in contending models of mitochondrial origin.

Proteins that participate in nucleotide excision repair of DNA in mammalian cells

1995 ◽  
Vol 347 (1319) ◽  
pp. 69-74 ◽  
Keyword(s):  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Binding Activity ◽  
Main Process ◽  
Base Pairs ◽  
Inherited Disorders ◽  
Dna Binding Activity ◽  
Nucleotide Excision ◽  
Repair Defect

The most versatile strategy for repair of damage to DNA, and the main process for repair of uv-induced damage, is nucleotide excision repair. In mammalian cells, the complete mechanism involves more than 20 polypeptides, and defects in many of these are associated with various forms of inherited disorders in humans. The syndrome xeroderma pigmentosum (XP) is associated with mutagen hypersensitivity and increased cancer frequency, and studies of the nucleotide excision repair defect in this disease have been particularly informative. Many of the XP proteins are now being characterized. XPA binds to DNA, with a preference for damaged base pairs. XPC activity is part of a protein complex with single-stranded DNA binding activity. The XPG protein is a nuclease.

scholarly journals The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cells

2004 ◽  
Vol 164 (7) ◽  
pp. 997-1007 ◽  
Author(s):  
Erik L. Snapp ◽  
Gretchen A. Reinhart ◽  
Brigitte A. Bogert ◽  
Jennifer Lippincott-Schwartz ◽  
Ramanujan S. Hegde
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Signal Recognition Particle ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Cellular Environment ◽  
Essential Components ◽  
Nascent Chain ◽  
Functional Components

Protein translocons of the mammalian endoplasmic reticulum are composed of numerous functional components whose organization during different stages of the transport cycle in vivo remains poorly understood. We have developed generally applicable methods based on fluorescence resonance energy transfer (FRET) to probe the relative proximities of endogenously expressed translocon components in cells. Examination of substrate-engaged translocons revealed oligomeric assemblies of the Sec61 complex that were associated to varying degrees with other essential components including the signal recognition particle receptor TRAM and the TRAP complex. Remarkably, these components not only remained assembled but also had a similar, yet distinguishable, organization both during and after nascent chain translocation. The persistence of preassembled and complete translocons between successive rounds of transport may facilitate highly efficient translocation in vivo despite temporal constraints imposed by ongoing translation and a crowded cellular environment.

Chemotherapy: induction of stress responses

2006 ◽  
Vol 13 (Supplement_1) ◽  
pp. S115-S124 ◽  
Author(s):  
E Tiligada
Keyword(s):  
Anticancer Agents ◽  
Stress Responses ◽  
Chemotherapeutic Agents ◽  
Clinical Value ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Shock Proteins ◽  
And Function ◽  
Protein Response ◽  
Functional Components

Eukaryotic cells, from yeast to mammals, respond and adapt to environmental and microenvironmental stressors by evolutionary conserved multicomponent endogenous systems that utilise a network of signal transduction pathways to regulate the adaptive and protective phenotype. The balance between cell survival and cell death is decisive for sensitivity or resistance to DNA-damaging chemotherapeutic agents. Anticancer drugs may themselves act as stressors to induce adaptive signals that could limit their clinical value. Related research has been focused on the modulation of the expression and function of the heat shock proteins, the unfolded protein response, the mechanisms of subcellular translocation of signalling components, the genomic and non-genomic actions of drugs and endogenous functional components like hormonal pathways, the input of inflammation and alterations in the microenvironmental milieu and on the control of the cell cycle and proliferation. The outcome seems to be driven by the first-line responses that support cellular integrity and by specific mechanisms that depend on the type of cell and the nature, and duration and severity of the noxious stimulus. Data obtained from experimental organisms like the yeast have added valuable information on the basic conservation in cellular stress-related processes in eukaryotes and on the consequences that may accompany the adaptive and protective phenotype during the stress response to anticancer agents. Understanding the complex molecular pathways mediating these processes has started to contribute to the reevaluation of the current therapeutic regiments and to revolutionise the approaches for improved anticancer therapy.

Metabolic rate does not scale with body mass in cultured mammalian cells

2007 ◽  
Vol 292 (6) ◽  
pp. R2115-R2121 ◽  
Author(s):  
Melanie F. Brown ◽  
Tyson P. Gratton ◽  
Jeffrey. A. Stuart
Keyword(s):  
Metabolic Rate ◽  
Body Mass ◽  
Oxygen Delivery ◽  
Mammalian Cells ◽  
Cultured Cells ◽  
Mammalian Species ◽  
Cellular Respiration ◽  
Metabolic Rates ◽  
Respiration Rates ◽  
Species Specific

The allometric scaling of metabolic rate with organism body mass can be partially accounted for by differences in cellular metabolic rates. For example, hepatocytes isolated from horses consume almost 10-fold less oxygen per unit time as mouse hepatocytes [Porter and Brand, Am J Physiol Regul Integr Comp Physiol 269: R226–R228, 1995]. This could reflect a genetically programmed, species-specific, intrinsic metabolic rate set point, or simply the adaptation of individual cells to their particular in situ environment (i.e., within the organism). We studied cultured cell lines derived from 10 mammalian species with donor body masses ranging from 5 to 600,000 g to determine whether cells propagated in an identical environment (media) exhibited metabolic rate scaling. Neither metabolic rate nor the maximal activities of key enzymes of oxidative or anaerobic metabolism scaled significantly with donor body mass in cultured cells, indicating the absence of intrinsic, species-specific, cellular metabolic rate set points. Furthermore, we suggest that changes in the metabolic rates of isolated cells probably occur within 24 h and involve a reduction of cellular metabolism toward values observed in lower metabolic rate organisms. The rate of oxygen delivery has been proposed to limit cellular metabolic rates in larger organisms. To examine the effect of oxygen on steady-state cellular respiration rates, we grew cells under a variety of physiologically relevant oxygen regimens. Long-term exposure to higher medium oxygen levels increased respiration rates of all cells, consistent with the hypothesis that higher rates of oxygen delivery in smaller mammals might increase cellular metabolic rates.

scholarly journals Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania major

2016 ◽  
Vol 60 (5) ◽  
pp. 2932-2940 ◽  
Author(s):  
Douglas R. Rice ◽  
Paola Vacchina ◽  
Brianna Norris-Mullins ◽  
Miguel A. Morales ◽  
Bradley D. Smith
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Mammalian Cells ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Coordination Complexes ◽  
Chemotherapeutic Agents ◽  
Selective Toxicity ◽  
Content Type

ABSTRACTCutaneous leishmaniasis is a neglected tropical disease that causes painful lesions and severe disfigurement. Modern treatment relies on a few chemotherapeutics with serious limitations, and there is a need for more effective alternatives. This study describes the selective targeting of zinc(II)-dipicolylamine (ZnDPA) coordination complexes towardLeishmania major, one of the species responsible for cutaneous leishmaniasis. Fluorescence microscopy ofL. majorpromastigotes treated with a fluorescently labeled ZnDPA probe indicated rapid accumulation of the probe within the axenic promastigote cytosol. The antileishmanial activities of eight ZnDPA complexes were measured using anin vitroassay. All tested complexes exhibited selective toxicity againstL. majoraxenic promastigotes, with 50% effective concentration values in the range of 12.7 to 0.3 μM. Similar toxicity was observed against intracellular amastigotes, but there was almost no effect on the viability of mammalian cells, including mouse peritoneal macrophages.In vivotreatment efficacy studies used fluorescence imaging to noninvasively monitor changes in the red fluorescence produced by an infection of mCherry-L. majorin a mouse model. A ZnDPA treatment regimen reduced the parasite burden nearly as well as the reference care agent, potassium antimony(III) tartrate, and with less necrosis in the local host tissue. The results demonstrate that ZnDPA coordination complexes are a promising new class of antileishmanial agents with potential for clinical translation.

The role of the p53 protein in the apoptotic response

1994 ◽  
Vol 345 (1313) ◽  
pp. 277-280 ◽  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Mammalian Cells ◽  
P53 Protein ◽  
P53 Gene ◽  
Chemotherapeutic Agents ◽  
Apoptotic Pathway ◽  
Cycle Arrest ◽  
Cell Death Pathway ◽  
Binding Function

When mammalian cells or tissues are exposed to DNA damaging agents a programmed cell death pathway is induced as well as a cell cycle arrest. In mice in which the p53 gene has been inactivated by homologous recombination this response is profoundly diminished. These mice develop normally so that developmentally induced apoptotic events do not require p53. The p53 gene product is a 393 amino acid nuclear protein that binds specifically to DNA and can act as a positive transcription factor. High levels of p53 can induce the transcription of gene products involved in the cell cycle arrest and apoptotic pathway. The p53 proteins activity is very tightly controlled both by allosteric regulation of its DNA binding function and by regulation of the protein’s stability. These results are discussed in the context of the mutations in p53 found in human tumours and their implications for the treatment of the disease by the use of radiation and chemotherapeutic agents that target DNA.

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