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New Molecular Insights in Mitochondrial Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 1625

Special Issue Editor

Special Issue Information

Dear Colleagues,

Pathogenetic role for mitochondrial dysfunction has been invoked in a growing number of illnesses without sufficient experimental support to precisely establish the molecular pathophysiological mechanisms. Indeed, mitochondrial physiology and pathophysiology are very complex, and the role of the organelles in bioenergetics is strictly linked to other essential functions such as anabolic pathways, redox balance, cell death and differentiation, and mitosis, along with more specialized cell functions including calcium homeostasis and thermogenesis, reactive oxygen species (ROS) and reactive nitric oxide species signalling, ion channels, and metabolite transporters. The same complexity and heterogeneity can be surmised from the range of congenital mitochondrial diseases, providing further evidence of the difficulty in correctly approaching mitochondrial pathophysiology. Importantly, this complexity caused a breaking up of mitochondrial research and consequently of specific literature in various and spuriously unrelated topics (mitochondria and calcium, mitochondria and apoptosis, mitochondria and oxidative phosphorylation, mitochondria and ROS, mitochondria and immunity, and so on) which further tangled a correct scientific approach.

At last but not least, mitochondria showed an intriguing pathogenetic roles in pathophysiology of COVID-19.

These unique aspects of mitochondria should stimulate to pay more attention than that usually devoted to both the pathological and clinical aspects related to these organelles. Moreover, their typical structural and functional characteristics may make mitochondria a valuable target for xenobiotics and this pathological interaction could have a significant role not only in potential novel therapeutic approaches but also in neglected iatrogenic diseases.

These intriguing and too often neglected different pathogenetic mechanisms push to better spread the knowledge of these various aspects of mitochondrial pathophysiology, to analyse and integrate such data to better spread their knowledge and so stimulate potential clinical applications in terms of diagnosis and above all of therapy.

Prof. Dr. Roberto Scatena
Guest Editor

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Published Papers (1 paper)

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Research

18 pages, 2749 KiB  
Article
NButGT Reinforces the Beneficial Effects of Epinephrine on Cardiac Mitochondrial Respiration, Lactatemia and Cardiac Output in Experimental Anaphylactic Shock
by Walid Oulehri, Antoine Persello, Angelique Blangy-Letheule, Charles Tacquard, Bertrand Rozec, Anne-Laure Charles, Bernard Geny, Benjamin Lauzier, Paul Michel Mertes and Olivier Collange
Int. J. Mol. Sci. 2024, 25(6), 3316; https://doi.org/10.3390/ijms25063316 - 14 Mar 2024
Cited by 2 | Viewed by 1232
Abstract
Anaphylactic shock (AS) is the most severe form of acute systemic hypersensitivity reaction. Although epinephrine can restore patients’ hemodynamics, it might also be harmful, supporting the need for adjuvant treatment. We therefore investigated whether NButGT, enhancing O-GlcNAcylation and showing beneficial effects in acute [...] Read more.
Anaphylactic shock (AS) is the most severe form of acute systemic hypersensitivity reaction. Although epinephrine can restore patients’ hemodynamics, it might also be harmful, supporting the need for adjuvant treatment. We therefore investigated whether NButGT, enhancing O-GlcNAcylation and showing beneficial effects in acute heart failure might improve AS therapy. Ovalbumin-sensitized rats were randomly allocated to six groups: control (CON), shock (AS), shock treated with NButGT alone before (AS+pre-Nbut) or after (AS+post-Nbut) AS onset, shock treated with epinephrine alone (AS+EPI) and shock group treated with combination of epinephrine and NButGT (AS+EPI+preNBut). Induction of shock was performed with an intravenous (IV) ovalbumin. Cardiac protein and cycling enzymes O-GlcNAcylation levels, mean arterial pressure (MAP), heart rate, cardiac output (CO), left ventricle shortening fraction (LVSF), mitochondrial respiration, and lactatemia were evaluated using Western blotting experiments, invasive arterial monitoring, echocardiography, mitochondrial oximetry and arterial blood samples. AS decreased MAP (−77%, p < 0.001), CO (−90%, p < 0.001) and LVSF (−30%, p < 0.05). Epinephrine improved these parameters and, in particular, rats did not die in 15 min. But, cardiac mitochondrial respiration remained impaired (complexes I + II −29%, p < 0.05 and II −40%, p < 0.001) with hyperlactatemia. NButGT pretreatment (AS+pre-Nbut) efficiently increased cardiac O-GlcNAcylation level as compared to the AS+post-Nbut group. Compared to epinephrine alone, the adjunction of NButGT significantly improved CO, LVSF and mitochondrial respiration. MAP was not significantly increased but lactatemia decreased more markedly. Pretreatment with NButGT increases O-GlcNAcylation of cardiac proteins and has an additive effect on epinephrine, improving cardiac output and mitochondrial respiration and decreasing blood lactate levels. This new therapy might be useful when the risk of AS cannot be avoided. Full article
(This article belongs to the Special Issue New Molecular Insights in Mitochondrial Medicine)
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