Defects in the Transport Mechanism of Membrane Proteins and Related Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 4154

Special Issue Editor

Department of Biosciences Biotechnology and Environment, University of Bari, Bari, Italy
Interests: structure/function relationship; transport mechanism; mitochondrial transport proteins; mitochondrial carrier diseases; mitochondrial carrier identification; design, synthesis and biological evaluation of new drugs against neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Membrane transport proteins play crucial roles across biological membranes and participate in cell physiology; metabolism and signaling; maintaining cellular homeostasis; and permitting the translocation of many classes of metabolites (i.e. sugar, amino acids, lipids, vitamins, inorganic ions and others). These proteins are essential for cellular functions ensuring cell survival in response to frequent stimuli of intracellular or environmental stress. Indeed, the transport mechanism exerted by membrane transport proteins, generating concentration gradients via active transport mechanisms, passive diffusion and ion channels, contributes to the regulation of biochemical pathways through correct cellular concentrations of substrates and products. Therefore, genetic mutations or the impairment of these transport systems could result in defects on transport mechanism with changes in the expression, activity and structure of proteins, which are manifested in different groups of neurodegenerative and metabolic diseases.

Hence, the purpose of this Special Issue “Defects in the Transport Mechanism of Membrane Proteins and Related Diseases" is to integrate current knowledge regarding physiological functions and the mechanisms of transport of a wide group of membrane transport proteins underlying their involvements in the initiation and progression of many diseases. Research papers and review manuscripts depicting a special focus on membrane transporters are cordially invited. Short communications will also be taken into consideration.

Dr. Daniela Valeria Miniero
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • function, structure and folding of membrane transport proteins
  • pathological mutations
  • mechanism of transport
  • neurological and metabolic disease
  • transport of nanoparticles
  • organelle membranes
  • cellular function and signaling
  • bioenergetics
  • neuroinflammation
  • nanoformulations for drug targets

Published Papers (3 papers)

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Research

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33 pages, 4147 KiB  
Article
Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue
by Sharon Natasha Cox, Claudio Lo Giudice, Anna Lavecchia, Maria Luana Poeta, Matteo Chiara, Ernesto Picardi and Graziano Pesole
Biomolecules 2024, 14(4), 411; https://doi.org/10.3390/biom14040411 - 28 Mar 2024
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Abstract
Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the [...] Read more.
Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS. Full article
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Review

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19 pages, 3459 KiB  
Review
Membrane Transporters Involved in Iron Trafficking: Physiological and Pathological Aspects
by Andrea Pasquadibisceglie, Maria Carmela Bonaccorsi di Patti, Giovanni Musci and Fabio Polticelli
Biomolecules 2023, 13(8), 1172; https://doi.org/10.3390/biom13081172 - 27 Jul 2023
Cited by 4 | Viewed by 1222
Abstract
Iron is an essential transition metal for its involvement in several crucial biological functions, the most notable being oxygen storage and transport. Due to its high reactivity and potential toxicity, intracellular and extracellular iron levels must be tightly regulated. This is achieved through [...] Read more.
Iron is an essential transition metal for its involvement in several crucial biological functions, the most notable being oxygen storage and transport. Due to its high reactivity and potential toxicity, intracellular and extracellular iron levels must be tightly regulated. This is achieved through transport systems that mediate cellular uptake and efflux both at the level of the plasma membrane and on the membranes of lysosomes, endosomes and mitochondria. Among these transport systems, the key players are ferroportin, the only known transporter mediating iron efflux from cells; DMT1, ZIP8 and ZIP14, which on the contrary, mediate iron influx into the cytoplasm, acting on the plasma membrane and on the membranes of lysosomes and endosomes; and mitoferrin, involved in iron transport into the mitochondria for heme synthesis and Fe-S cluster assembly. The focus of this review is to provide an updated view of the physiological role of these membrane proteins and of the pathologies that arise from defects of these transport systems. Full article
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16 pages, 4415 KiB  
Review
Small Molecules Targeting Kidney ClC-K Chloride Channels: Applications in Rare Tubulopathies and Common Cardiovascular Diseases
by Maria Antonietta Coppola, Michael Pusch, Paola Imbrici and Antonella Liantonio
Biomolecules 2023, 13(4), 710; https://doi.org/10.3390/biom13040710 - 21 Apr 2023
Cited by 1 | Viewed by 1793
Abstract
Given the key role played by ClC-K chloride channels in kidney and inner ear physiology and pathology, they can be considered important targets for drug discovery. Indeed, ClC-Ka and ClC-Kb inhibition would interfere with the urine countercurrent concentration mechanism in Henle’s loop, which [...] Read more.
Given the key role played by ClC-K chloride channels in kidney and inner ear physiology and pathology, they can be considered important targets for drug discovery. Indeed, ClC-Ka and ClC-Kb inhibition would interfere with the urine countercurrent concentration mechanism in Henle’s loop, which is responsible for the reabsorption of water and electrolytes from the collecting duct, producing a diuretic and antihypertensive effect. On the other hand, ClC-K/barttin channel dysfunctions in Bartter Syndrome with or without deafness will require the pharmacological recovery of channel expression and/or activity. In these cases, a channel activator or chaperone would be appealing. Starting from a brief description of the physio-pathological role of ClC-K channels in renal function, this review aims to provide an overview of the recent progress in the discovery of ClC-K channel modulators. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Theoretical and experimental insights into the Inhibition of Purified Rat Brain 2-Oxoglutarate Carrier by Hemin
Authors: Daniela Valeria Miniero
Affiliation: University of Bari - Department of Biosciences, Biotechnologies and Biopharmaceutics Via Orabona 4 Bari-Italy
Abstract: A new kinetic analysis of the transport assays of the purified Rat Brain 2-Oxoglutarate carrier was performed starting from the results showing a competitive inhibitory behaviour of hemin, a phys-iological porphirine derivative, on the 2-oxoglutarate/malate antiport, catalyzed by the mito-chondrial 2-oxoglutarate carrier, isolated from rat brain mitochondria and reconstituted in an active form into proteoliposomes. In the light of the new elaboration of the kinetic equation, the data clearly support the hypothesis that hemin shows a partially competitive inhibition, instead of a pure competitive inhibition, with the formation of a ternary complex consisting of “he-min-carrier-substrate”. A possible interpretation of the provided kinetic analysis was also supported by computational studies, allowing to propose a regulation binding region located on OGC mito-chondrial matrix loops, where hemin can establish interactions with residues involved in the sub-strate recognition and/or conformational changes responsible for the translocation of mitochondrial carrier substrates. Such regulation site is placed about 10 Å from the binding site and enables the simultaneous binding of hemin and 2-oxoglutarate or malate within the carrier. Overall, the ex-perimental and computational analysis helped to shed light on the possible structure of the proposed “hemin-carrier-substrate complex”.

Title: To be confirmed
Authors: Nancy J. Philp
Affiliation: Department of Pharmacology and Experimental Therapeutics, Sydney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States

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