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Targeting Mitochondria in Metabolic Diseases 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 12088

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Special Issue Editors

Prof. Dr. Carlos Palmeira

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Guest Editor

Department of Life Sciences and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
Interests: liver; muscle; adipose tissue; ischemia/reperfusion; mitochondria; steatosis; mitochondrial signaling and bioenergetics; mitochondrial dynamics; mitohormesis
Special Issues, Collections and Topics in MDPI journals

Dr. Anabela P. Rolo

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Guest Editor

Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
Interests: PCR; electrophoresis; gene expression; molecular biology; cell biology; biochemistry; signal transduction; Western blot; oxidative stress; signaling pathways; liver diseases; mitochondria bioenergetics; mitochondria isolation; liver mitochondria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Several alterations in mitochondrial morphology, structure, and function have been associated with pathologic conditions characterized by metabolic alterations. The maintenance of mitochondrial homeostasis requires both the clearance of damaged organelles and the recovery of mitochondrial mass and function. Therefore, an imbalance between mitochondrial biogenesis and mitophagy in response to cellular metabolic state, stress, and other intracellular or environmental signals disrupts energy metabolism. Post-translational modifications of mitochondrial proteins are also critical to the regulation of redox status and metabolism.

Alterations in lifestyle (nutrition and exercise) and pharmacological interventions have been shown to promote mitochondrial homeostasis by acting on metabolic sensors such as sirtuins (SIRTs) and AMP kinase (AMPK). For instance, caloric restriction, while reducing the concentration of glucose, amino acids, and lipids, raises the concentration of metabolic effectors such as nicotinamide adenine dinucleotide (NAD+) and adenosine monophosphate (AMP). Additionally, age-dependent decline in NAD+ results in the decrease of SIRT1 activity, ultimately through a failure in mitochondrial homeostasis.

We aim to highlight new areas of research focused on the study of mitochondrial alterations and pathways which may improve predictable changes in mitochondrial physiology (mitochondrial mass, gene expression, and cellular ATP concentration) and a greater susceptibility to age/metabolic-related diseases.

Prof. Dr. Carlos Palmeira
Dr. Anabela P. Rolo
Guest Editors

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mitochondria
mitophagy
metabolic disease
exercise
mitochondrial biogenesis
redox status
metabolic sensors

Published Papers (4 papers)

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Research

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17 pages, 2963 KiB

Open AccessArticle

Gestational Exercise Increases Male Offspring’s Maximal Workload Capacity Early in Life

by Jorge Beleza, Jelena Stevanović-Silva, Pedro Coxito, Hugo Rocha, Paulo Santos, António Ascensão, Joan Ramon Torrella and José Magalhães

Int. J. Mol. Sci. 2022, 23(7), 3916; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073916 - 01 Apr 2022

Cited by 2 | Viewed by 1581

Abstract

Mothers’ antenatal strategies to improve the intrauterine environment can positively decrease pregnancy-derived intercurrences. By challenging the mother–fetus unit, gestational exercise (GE) favorably modulates deleterious stimuli, such as high-fat, high-sucrose (HFHS) diet-induced adverse consequences for offspring. We aimed to analyze whether GE alters maternal HFHS-consumption effects on male offspring’s maximal workload performance (MWP) and in some skeletal muscle (the soleus—SOL and the tibialis anterior—TA) biomarkers associated with mitochondrial biogenesis and oxidative fitness. Infant male Sprague-Dawley rats were divided into experimental groups according to mothers’ dietary and/or exercise conditions: offspring of sedentary control diet-fed or HFHS-fed mothers (C–S or HFHS–S, respectively) and of exercised HFHS-fed mothers (HFHS–E). Although maternal HFHS did not significantly alter MWP, offspring from GE dams exhibited increased MWP. Lower SOL AMPk levels in HFHS–S were reverted by GE. SOL PGC-1α, OXPHOS C-I and C-IV subunits remained unaltered by maternal diet, although increased in HFHS–E offspring. Additionally, GE prevented maternal diet-related SOL miR-378a overexpression, while upregulated miR-34a expression. Decreased TA C-IV subunit expression in HFHS–S was reverted in HFHS–E, concomitantly with the downregulation of miR-338. In conclusion, GE in HFHS-fed dams increases the offspring’s MWP, which seems to be associated with the intrauterine modulation of SM mitochondrial density and functional markers. Full article

(This article belongs to the Special Issue Targeting Mitochondria in Metabolic Diseases 2.0)

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16 pages, 2010 KiB

Open AccessArticle

PEG35 as a Preconditioning Agent against Hypoxia/Reoxygenation Injury

by Rui Teixeira da Silva, Ivo F. Machado, João S. Teodoro, Arnau Panisello-Roselló, Joan Roselló-Catafau, Anabela P. Rolo and Carlos M. Palmeira

Int. J. Mol. Sci. 2022, 23(3), 1156; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031156 - 21 Jan 2022

Cited by 7 | Viewed by 2059

Abstract

Pharmacological conditioning is a protective strategy against ischemia/reperfusion injury, which occurs during liver resection and transplantation. Polyethylene glycols have shown multiple benefits in cell and organ preservation, including antioxidant capacity, edema prevention and membrane stabilization. Recently, polyethylene glycol 35 kDa (PEG35) preconditioning resulted in decreased hepatic injury and protected the mitochondria in a rat model of cold ischemia. Thus, the study aimed to decipher the mechanisms underlying PEG35 preconditioning-induced protection against ischemia/reperfusion injury. A hypoxia/reoxygenation model using HepG2 cells was established to evaluate the effects of PEG35 preconditioning. Several parameters were assessed, including cell viability, mitochondrial membrane potential, ROS production, ATP levels, protein content and gene expression to investigate autophagy, mitochondrial biogenesis and dynamics. PEG35 preconditioning preserved the mitochondrial function by decreasing the excessive production of ROS and subsequent ATP depletion, as well as by recovering the membrane potential. Furthermore, PEG35 increased levels of autophagy-related proteins and the expression of genes involved in mitochondrial biogenesis and fusion. In conclusion, PEG35 preconditioning effectively ameliorates hepatic hypoxia/reoxygenation injury through the enhancement of autophagy and mitochondrial quality control. Therefore, PEG35 could be useful as a potential pharmacological tool for attenuating hepatic ischemia/reperfusion injury in clinical practice. Full article

(This article belongs to the Special Issue Targeting Mitochondria in Metabolic Diseases 2.0)

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14 pages, 2429 KiB

Open AccessArticle

Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes

by Anna F. Bekebrede, Thirza van Deuren, Walter J. J. Gerrits, Jaap Keijer and Vincent C. J. de Boer

Int. J. Mol. Sci. 2021, 22(20), 10937; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010937 - 10 Oct 2021

Cited by 4 | Viewed by 2211

Abstract

Butyrate is considered the primary energy source of colonocytes and has received wide attention due to its unique health benefits. Insight into the mechanistic effects of butyrate on cellular and metabolic function relies mainly on research in in-vitro-cultured cells. However, cells in culture differ from those in vivo in terms of metabolic phenotype and nutrient availability. For translation, it is therefore important to understand the impact of different nutrients on the effects of butyrate. We investigated the metabolic consequences of butyrate exposure under various culturing conditions, with a focus on the interaction between butyrate and glucose. To investigate whether the effects of butyrate were different between cells with high and low mitochondrial capacity, we cultured HT29 cells under either low- (0.5 mM) or high- (25 mM) glucose conditions. Low-glucose culturing increased the mitochondrial capacity of HT29 cells compared to high-glucose (25 mM) cultured HT29 cells. Long-term exposure to butyrate did not alter mitochondrial bioenergetics, but it decreased glycolytic function, regardless of glucose availability. In addition, both high- and low-glucose-grown HT29 cells showed increased lipid droplet accumulation following long-term butyrate exposure. Acute exposure of cultured cells (HT29 and Caco-2) to butyrate increased their oxygen consumption rate (OCR). A simultaneous decrease in extracellular acidification rate (ECAR) was observed. Furthermore, in the absence of glucose, OCR did not increase in response to butyrate. These results lead us to believe that butyrate itself was not responsible for the observed increase in OCR, but, instead, butyrate stimulated pyruvate flux into mitochondria. Indeed, blocking of the mitochondrial pyruvate carrier prevented a butyrate-induced increase in oxygen consumption. Taken together, our results indicate that butyrate itself is not oxidized in cultured cells but instead alters pyruvate flux and induces lipid accumulation. Full article

(This article belongs to the Special Issue Targeting Mitochondria in Metabolic Diseases 2.0)

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Review

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54 pages, 991 KiB

Open AccessReview

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed

by Alina M. Bețiu, Lavinia Noveanu, Iasmina M. Hâncu, Ana Lascu, Lucian Petrescu, Christoph Maack, Eskil Elmér and Danina M. Muntean

Int. J. Mol. Sci. 2022, 23(21), 13653; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113653 - 07 Nov 2022

Cited by 13 | Viewed by 5406

Abstract

Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature. Full article

(This article belongs to the Special Issue Targeting Mitochondria in Metabolic Diseases 2.0)

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