Current Molecular Medicine (CURR MOL MED )

Publisher: Bentham Science Publishers

Description

Current Molecular Medicine is a bimonthly, interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

  • Impact factor
    4.20
    Show impact factor history
     
    Impact factor
  • 5-year impact
    4.64
  • Cited half-life
    5.00
  • Immediacy index
    0.72
  • Eigenfactor
    0.01
  • Article influence
    1.48
  • Website
    Current Molecular Medicine website
  • Other titles
    Current molecular medicine (Online)
  • ISSN
    1566-5240
  • OCLC
    55201263
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Bentham Science Publishers

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months (unless federal, government, funding agencies or local policy mandates for the author's institute a different policy on self-archiving)
  • Conditions
    • On authors personal or authors institutions server
    • Published source must be acknowledged
    • Must link to journal home page
    • Publisher's version/PDF cannot be used
    • Articles in all journals can be made Open Access on payment of additional charge
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the past few years it has become clear that mitochondria are not merely the powerhouses of cells. Proteome-analyses of mitochondria from different organisms and organs revealed that more than 1000 proteins are localized in and/or on mitochondria. This by far exceeds the number of proteins required for classical mitochondrial functions, e.g. the respiratory chain, the tricarboxylic acid cycle, fatty acid oxidation and apoptosis. This suggests that many of these proteins have other, as yet unknown functions. Several proteins with well-described nuclear functions, like the transcription factor FoxO3A or the Telomerase Reverse Transcriptase, have recently been shown to be localized also within the mitochondria. This mini-review will focus on the description of the functions of these two proteins in the nucleus and in the mitochondria - as two examples of many more proteins, which are yet to be uncovered. It will give insights into the role of these proteins within different organelles of the cell and will reveal that the functions of the proteins are probably not the same in the nucleus and the mitochondria. Therefore, these differences have to be considered when targeting proteins for therapeutic approaches.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: The domestic horse is the most widely used and important stock and recreational animal, valued for its strength and endurance. The energy required by the domestic horse is mainly supplied by mitochondria via oxidative phosphorylation. Thus, selection may have played an essential role in the evolution of the horse mitochondria. Besides, demographic events also affect the DNA polymorphic pattern on mitochondria. To understand the evolutionary patterns of the mitochondria of the domestic horse, we used a deep sequencing approach to obtain the complete sequences of 15 mitochondrial genomes, and four mitochondrial gene sequences, ND6, ATP8, ATP6 and CYTB, collected from 509, 363, 363 and 409 domestic horses, respectively. Evidence of strong substitution rate heterogeneity was found at nonsynonymous sites across the genomes. Signatures of recent positive selection on mtDNA of domestic horse were detected. Specifically, five amino acids in the four mitochondrial genes were identified as the targets of positive selection. Coalescent-based simulations imply that recent population expansion is the most probable explanation for the matrilineal population history for domestic horse. Our findings reveal a complex pattern of non-neutral evolution of the mitochondrial genome in the domestic horses.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: Diploid natural gynogenetic goldfish (2nGRCG), triploid hybrids (3nRB) and tetraploid hybrids (4nRB) are generated by distant hybridization of red common goldfish (RCG, Carassius auratus red var.) and blunt snout bream (BSB, Megalobrama amblycephala). In the present study, we obtained the complete mitochondrial DNA (mtDNA) sequences of the hybrid offspring and compared them with the homologous sequences of RCG and BSB. All mtDNA sequences of these hybrids were 16,580bp in length, and the genes number, size, and order were quite similar to that of RCG. Genetic analysis revealed that the mtDNA sequences of these hybrids had high similarity (>99%) and low divergence (<2%) to their maternal RCG, yet lower similarities (84%) and higher divergences (16%) to their paternal BSB. The phylogenetic analysis also showed that the sequences of 2nGRCG, 3nRB and 4nRB were clustered with RCG rather than with BSB. These results indicate that the mitochondrial genomes of 2nGRCG, 3nRB and 4nRB remain maternally inherited after hybridization and polyploidization. Moreover, clade separation of hybrid offspring from their BSB in the phylogenetic tree implies that phylogenetic analysis of mtDNA is incomplete for elucidating the true relationships between different species, particularly when they have undergone hybridization or allopolyploidization. Our study provides significant information for both evolution and genetic studies of mtDNA for hybrid species and allopolyploidization species.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: It has been suggested that impairment of mitochondrial oxidative phosphorylation (OXPHOS) is a common character in cancer cells, urging attention to variation on mitochondrial DNA (mtDNA) that encodes 13 units of the OXPHOS. However, most of mtDNA somatic mutations in cancer were suggested to result from the relaxed functional constrains and thus the byproducts of tumorigenesis. MtDNA germline mutations present not only in the cancer tissue but also in the normal tissue. However, it remains unclear whether the cancerous mtDNA germline mutations suffered similar selective constraints as the somatic mutations did. To address this question, we collected 153 whole mitochondrial genomes (including 20 newly obtained genomes in this study) from the normal tissues of cancer patients and compared with a number of 561 whole mtDNA sequences from the general population in China. Different from the observations on cancerous mtDNA somatic mutations, our results revealed that the germline mutations showed no significant difference between the cancer patients and the general population in either the sub-haplogroup composition, mutation pattern or the potential pathogenicity of the private mutations. It then seems that regulation on cellular OXPHOS level, triggered by mtDNA variation to some extent, exerts little influence on the susceptibility of cancer, which echoes the opinion that aerobic glycolysis, not mitochondrial respiration, plays the key role in generating energy in cancer cells, thus suggesting the role of most mtDNA mutations in cancer likely being overestimated.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: Malignant melanoma (MM) is one of the most lethal tumors and is characterized by high invasiveness, frequent metastasis, and resistance to chemotherapy. The risk of metastatic MM is accompanied by disordered energy metabolism involving the oxidative phosphorylation (OXPHOS) process, which is largely carried out in mitochondrial complexes. Complex I is the first and largest mitochondrial enzyme complex associated with this process. CD147 is a transmembrane glycoprotein mainly expressed on the cell surface, and also appears in the cytoplasm in some tumors. We found that CD147 is often translocated to the cytoplasm in metastatic MM specimens as compared to primary MM. We also demonstrated high expression of CD147 in isolated mitochondrial fractions of A375 cells. The yeast two-hybrid (Y2H) assay identified NDUFS6 (which encodes a subunit of mitochondrial respiratory chain complex I) as a candidate that interacts with CD147 and depletion of CD147 in A375 cells significantly decreased complex I enzyme activity. We also showed that CD147 increased the viability of A375 cells exposed to berberine-induced mitochondrial damage, and protected them from apoptosis through a mitochondrial-dependent pathway. This finding was confirmed by adding exogenous Bcl-2 to A375 cell cultures. In summary, our results identify the existence of CD147 in human melanoma cell mitochondria. They indicate that CD147 appears to regulate complex I activity and apoptosis in MM by interacting with mitochondrial NDUFS6. Our findings provide new insight into the function of CD147 and identify it as a promising therapeutic target in melanoma through disruption of the energy metabolism.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: The role of mitochondrial DNA (mtDNA) variant 16189T>C in type 2 diabetes mellitus (T2DM) remains hotly debated in the past decade. If mutation 16189T>C indeed posed a risk to T2DM, as echoed by some recent studies, correlation between this mutation and disease should be observed when carrying out a systematical study using data and samples collected in a large geographic region in China. To test this hypothesis, we first performed a linear regression analysis between the prevalence of T2DM and the allele frequency of 16189C variant in 10 East Asian populations, and further genotyped this variant in two case-control cohorts from west Han Chinese (Kunming and Xining). Linear regression analysis showed that no significant correlation was observed (r2=0.211, P=0.181), and the genotyping results indicated that the m.16189T>C frequency difference between case and control was not significant in either populations (P=0.38 and 0.89 for Kunming and Xining, respectively). Matrilineal backgrounds constitution (in terms of haplogroups) analysis generated a similar haplogroup distribution in both populations (P>0.1). All results failed to substantiate that m.16189T>C may play an active role in the development of T2DM in East Asian populations.
    Current Molecular Medicine 12/2014;
  • Current Molecular Medicine 12/2014;
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    ABSTRACT: The genus Paedocypris is a newly described taxon of minifish species that are characterized by extensive chromosome evolution, one of the smallest known vertebrate nuclear genomes. Paedocypris features a tiny adult size, a short generation time, low fecundity and fragmented tropical habitats, which are factors that favor rapid speciation. Most recently, we have revealed that P. progenetica (Pp), the type species of the genus Paedocypris, has an unusual mtDNA bearing - within its D-loop - a tandem array of a 34-bp repeat sequence called the minifish repeat, which shows compromised replication efficiency in vitro. Here we report that Pp exhibits high genetic variation in mtDNA size. The efficiency of D-loop amplification was found to depend upon primers. Interestingly, Pp individuals of one and the same population differed drastically in mtDNA size resulting from varying copy numbers of the minifish repeat. We conclude that minifish has a high mutation rate and perhaps represents a rapidly evolving taxon of vertebrates.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: Sinipercids are a group of freshwater perciform fish endemic in East Asia with the majority of species recorded in China. In the present study, we analyzed the organizations of complete mitogenomes of the six sinipercid fish populations from the Yangtze River and the Pearl River systems in China. The proportion of G was relatively low just at 16.2%-16.5% among the fish populations analyzed. The similarity and divergence analysis showed that the populations from different drainages have more sequence similarities than those from different species in the same drainages. The rate of point mutation was 0.39% and a total of 422 variable sites were identified in the 12 protein-coding genes (excluding the ND6) among the four S. scherzeri populations. The analysis of evolutionary relationship showed that the four S. scherzeri populations can be divided into two groups of Yangtze River system and the Pearl River. Overall the data provide significant information for the genetic and evolutionary status of sinipercids upon adapting to different environments, and for genetic conversation and selective breeding of these fish species in fishery and aquaculture.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: An allotetraploid hybrid lineage derived from the distant hybridization of red crucian carp (Carassius auratus red var., ♀, 2n =100) × common carp (Cyprinus carpio L., ♂, 2n =100) was investigated for its mitochondrial and nuclear genome inheritance patterns. Based on liver transcriptomic data for this hybrid, red crucian carp, and common carp, we identified 94, 136, and 86 contigs corresponding to 41, 46, and 37 mitochondrial respiratory chain nuclear genes, respectively. Mitochondrial respiratory chain nuclear gene sequences from red crucian carp and common carp were both detected in the allotetraploid hybrid, indicating that both parental nuclear genomes had participated in the synthesis of mitochondrial respiratory protein complexes in the hybrid. For mitochondrial respiratory related genes, high sequence similarity (>90%) and a low nucleotide divergence rate (<0.2) between red crucian carp and common carp could be a critical factor allowing cooperation of the three genomes (red crucian carp mitochondrial genome, red crucian and common carp nuclear genomes) in the hybrid lineage. Interestingly, gene duplication events were identified in the allotetraploid hybrid, red crucian and common carp, as confirmed by analysis of orthologous gene trees for these fish. Our findings provide valuable information with which to study cooperation between the nuclear and mitochondrial genomes of other hybrids, and will provide basic genetic information of relevance to mitochondrial-related diseases in humans and animals.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: Paedocypris is a newly described minifish genus endemic to Southeast Asia. Besides a tiny adult size of ~8 mm in length, minifish feature fragmentary habitats of acidic peat blackwater swamps, an unusual reproduction mode, truncated development and is the smallest known vertebrate genome. A complete sequence is absent for the minifish mitochondrial DNA (mtDNA). Here we report the complete mtDNA sequence and its unusual feature in the minifish P. progenetica (Pp). We show that the Pp mtDNA is a circular molecule of 17,382 bp in length and has the same number of similarly oriented genes as in other vertebrates. Specifically, it comprises 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 D-loop. Surprisingly, the D-loop is elusive for amplification by standard PCR conditions. The D-loop possesses a 28-bp dinucleotide TA repeat and more intriguingly, up to 25 copies of a 34-bp tandem repeat sequence. These tandem repeats predict the formation of paired regions. Hence, besides a generally conserved mtDNA with other vertebrates, the Pp mtDNA features an unusual D-loop and compromised DNA replication in vitro.
    Current Molecular Medicine 12/2014;
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    ABSTRACT: The identification of allopolyploidization events benefits from molecular dating and divergence assessments of progenitor genomes. Information on gene duplications only, either orthologs or paralogs, provides incomplete information. Analyses of mitochondrial DNA yield insights into matrilineal history, which may differ from patrilineal evolution. Two important food and pet fishes, the common carp (Cyprinus carpio) and goldfish (Carassius sp.), appear to have experienced allotetraploidization sometime from 12 to 20 million years ago (Ma). However, much work is necessary to detail the initial polyploidization event. Herein, we use this group of fishes as a model system to investigate competing scenarios for allopolyploidization. We analyze both the nuclear genes encoding growth hormone (GH), recombination activating protein 1 (Rag1) and HoxA2b gene, and the maternal heredited 12 concatenated mitochondrial protein-coding gene in 19 species of cyprinids and use two species in Balitoridae as outgroup taxa. Our analyses clarify the phylogenetic position of the paternal and maternal ancestors for the common carp and goldfish. The estimation of matrilineal divergence (10.71-12.42 Ma) is significantly younger than the dates of the parental ancestor divergedthat obtained by nuclear genes (16.62-19.64 Ma). Analyses of both genomes date the allopolyploidization event of the common ancestor of Cy. carpio and Ca sp. to about 10.71-12.42 Ma, which is most likely represented by maternal divergent time. The divergence of the two copies of the nuclear genes which was more ancient than the maternal markers might have been included the divergence of the progenitors' genome divergence when the allopolyploidization event occurred. Thus, the scenarios of allopolyploidzation for this group of fish can be suggested as the following: the matrilineal common ancestor of species in tribe Cyprinini might have doubled its genome by mating with a paternal ancestor in the subfamily Cyprininae, which was a sister-group that diverged around 4.20-8.93 Ma. Our work provides new evidence for the divergence dates of allopolyploidization within the Cyprinini, and documents the necessity of considering both matrilineal and patrilineal histories when investigating allopolyploidization.
    Current Molecular Medicine 12/2014;
  • Current Molecular Medicine 12/2014; 14(10).
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    ABSTRACT: The hereditary spastic paraplegias (HSP) are characterized by spastic gait with weakness in the legs and additional neurological or extra-neurological signs in "complicated" forms. The past two decades have witnessed major advances in our understanding of their molecular bases with the identification of a plethora of loci and the cloning of several SPG genes. Combined genetic and clinical information has permitted a modern, molecularly-driven classification and an improved diagnosis, with several new data on the possible disease mechanisms. Further heterogeneity will rapidly emerge with the diffusion of next-generation sequencing platforms and, under the shadow of common themes in the pathogenesis, new therapeutic options will likely emerge for a great number of patients.
    Current Molecular Medicine 09/2014; 14(8).
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    ABSTRACT: Mitochondrial disorders are a group of heterogeneous diseases associated with abnormalities of the oxidative phosphorylation (OXPHOS), the most important source of energy for the cell. The number of mitochondrial syndromes and of identified causative genes is constantly increasing. Taken as a whole they are among the most frequent genetic diseases in humans at any age. The respiratory chain is the only metabolic pathway under double genome control and molecular genetics of these disorders is complicated by the existence of strict interactions between mitochondrial DNA and nuclear DNA. In childhood and infancy, clinical presentation differs from mitochondrial disorders with adult onset. The phenotypes are much more severe, often involving brain, frequently presenting as multisystemic disorders and seldom as isolated myopathy. Mutations in nDNA are more frequent than in adulthood. The major phenotypes presenting in infancy are here correlated with genetic defects and biochemical data with the aim to facilitate diagnosis work-up.
    Current Molecular Medicine 09/2014; 14(8).
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    ABSTRACT: Mitochondrial Disorders (MD) include a heterogeneous group of inherited disorders due to molecular defects mainly affecting the mitochondrial oxidative phosphorylation system. Because the respiratory chain is under control of two different genomes (nuclear DNA-nDNA and mitochondrial DNA-mtDNA), mitochondrial genetics is quite complex and may justify the extreme clinical heterogeneity of these diseases. Clinically, MD usually involve multiple tissues, mainly affecting organs with high energy request as central nervous system and skeletal muscle. They may present at any age, with different onsets, clinical presentation and progression from an isolated involvement of vision or hearing to a multisystemic degenerative disorders with stroke-like episodes, peripheral neuropathy, ophthalmoparesis, seizures, cardiopathy, hepatopathy, endocrinopathies, etc. Over the last 50 years, it became evident that MD represent an important part of the general medicine. The complexity of clinical and genetic spectrum of those disorders is still increasing. The aim of this review is to walk through mitochondrial genetics, highlighting novel clinical entities.
    Current Molecular Medicine 09/2014; 14(8).
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    ABSTRACT: In the last twenty years the rapid advances in neurogenetic have revolutionized not only the molecular, pathological, inheritance but also the clinical concept of ALS. Here we review the current genetic breakthrough in familial and sporadic ALS, considering how this knowledge has allowed widening of the scenario on the possible pathogenic disease mechanisms and better understanding of the relationship between the genetic, pathological and clinical subtypes.
    Current Molecular Medicine 09/2014; 14(8).
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    ABSTRACT: Limb girdle muscular dystrophies (LGMD) are a heterogeneous group of inherited progressive muscle disorders affecting predominantly the shoulder and pelvic girdle muscles. They present both with autosomal dominant and autosomal recessive patterns of inheritance. Recent development, including results from Next Generation Sequencing technology, expanded the number of recognised forms. Therefore a revised genetic classification that takes into account the novel entities is needed, allowing clinicians and researchers to refer to a common nomenclature for diagnostic and research purposes.
    Current Molecular Medicine 09/2014; 14(8).
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    ABSTRACT: The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers. Compounding this matter even further, reports of increased cardiovascular risk associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, have revealed additional and unforeseen contributors to myocardial infarction and stroke. With all medications, striking a balance between the potential risks and benefits seems more art than science at times. However, given their widespread use and critical cardiovascular implications, further emphasis has been placed on understanding factors influencing antithrombotic and NSAID therapies. A major aim in cardiovascular pharmacogenetics is the discovery of genetic biomarkers that will allow for prospective screening and individualized prediction of drug efficacy and adverse reactions for these medications (both alone and together) within the context of cardiovascular disease.
    Current Molecular Medicine 08/2014;
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    ABSTRACT: Recent changes to the clinical management guidelines for hypertension and hyperlipidemia have placed emphasis on prevention through the pharmacological control and reduction of cardiovascular risk factors. In conjunction with proper diet and lifestyle changes, such risk factor control necessitates the use of safe and effective pharmacotherapy. However, many patients fail to reach or maintain therapeutic goals due to inadequacy and/or variability in response to antihypertensive and lipid-lowering medications. Thus, given the contribution of both hypertension and hyperlipidemia in the development and progression of cardiovascular disease, a personalized approach to pharmacotherapy, as well as disease prevention, seems particularly prudent. With the advancement of cardiovascular pharmacogenetics, the aim is to identify genetic biomarkers of drug-response and disease-susceptibility in order to make informed and individualized decisions, improving patient care through proper drug selection and dosing.
    Current Molecular Medicine 08/2014;