International Journal of Molecular Sciences

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Dear Colleagues,

New developments in the field of genetic methodology and molecular techniques have allowed us to recognize mitochondrial disorders as more complex and multifactorial than originally thought. At present, the terms “primary mitochondrial disease” and “secondary mitochondrial dysfunction” have been widely used to characterize mitochondrial pathophysiology. Primary mitochondrial diseases are clinically heterogeneous diseases associated with changes in genetic material (e.g., deletions, depletions, mutations) within the DNA of mitochondria (mtDNA) or cell nuclei (nDNA), affecting mainly nervous and muscular tissues. Beyond the disorders recognized as mitochondrial diseases, abnormalities in the ultrastructure and function of mitochondria in cells have been revealed in a number of unrelated pathologies. These include diabetes mellitus, cardiovascular pathologies, myopathies, cancers, organ-specific (e.g., eye or liver) disorders, ageing, as well as neurologic and immune diseases. In addition, multiple lines of evidence have suggested mitochondrial dysfunction as a mechanism for pharmaceutical-drug-induced toxicity in the heart, brain, liver, and other organs and tissues. The accumulated knowledge in these areas requires research aimed at clarifying open questions.

This Special Issue is focused on the molecular and cellular mechanisms leading to mitochondrial disorders, with particular attention to molecules involved in the regulation of mitochondrial dynamics, biogenesis, and mitophagy. Especially, studies employing novel therapeutic approaches targeting mitochondria and redox dyshomeostasis to improve treatment outcomes will be given priority. Additionally, research papers and review articles exploring the effects of mitochondrial therapy on cell pathologies will also be included.

Prof. Dr. Konstantin Belosludtsev
Guest Editor

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Keywords

mitochondria
mitochondrial DNA
mitochondrial dynamics
mitophagy
mitochondrial toxicity
apoptosis
primary mitochondrial disease
secondary mitochondrial dysfunction
mitochondria-targeted drug discovery

Published Papers (2 papers)

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Research

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12 pages, 1603 KiB

Open AccessCommunication

Alterations in Mitochondrial Morphology and Quality Control in Primary Mouse Lung Microvascular Endothelial Cells and Human Dermal Fibroblasts under Hyperglycemic Conditions

by Natalia V. Belosludtseva, Dmitriy A. Serov, Vlada S. Starinets, Nikita V. Penkov and Konstantin N. Belosludtsev

Int. J. Mol. Sci. 2023, 24(15), 12485; https://doi.org/10.3390/ijms241512485 - 06 Aug 2023

Viewed by 1117

Abstract

The effect of hyperglycemia on the morphology of individual mitochondria and the state of the mitochondrial network in primary mouse lung microvascular endotheliocytes and human dermal fibroblasts has been investigated. The cells were exposed to high (30 mM) and low (5.5 mM) glucose concentrations for 36 h. In primary endotheliocytes, hyperglycemic stress induced a significant increase in the number of mitochondria and a decrease in the interconnectivity value of the mitochondrial network, which was associated with a decrease in the mean size of the mitochondria. Analysis of the mRNA level of the genes of proteins responsible for mitochondrial biogenesis and mitophagy revealed an increase in the expression level of the Ppargc1a, Pink1, and Parkin genes, indicating stimulated mitochondrial turnover in endotheliocytes under high glucose conditions. In primary fibroblasts, hyperglycemia caused a decrease in the number of mitochondria and an increase in their size. As a result, the mitochondria exhibited higher values for elongation. In parallel, the mRNA level of the Ppargc1a and Mfn2 genes in fibroblasts exposed to hyperglycemia was reduced. These findings indicate that high glucose concentrations induced cell-specific morphological rearrangements of individual mitochondria and the mitochondrial network, which may be relevant during mitochondria-targeted drug testing and therapy for hyperglycemic and diabetic conditions. Full article

(This article belongs to the Special Issue Primary Mitochondrial Diseases and Secondary Mitochondrial Dysfunction: New Insights and Therapies)

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Review

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24 pages, 1356 KiB

Open AccessReview

Mitochondrial Dyshomeostasis as an Early Hallmark and a Therapeutic Target in Amyotrophic Lateral Sclerosis

by Natalia V. Belosludtseva, Lyudmila A. Matveeva and Konstantin N. Belosludtsev

Int. J. Mol. Sci. 2023, 24(23), 16833; https://doi.org/10.3390/ijms242316833 - 27 Nov 2023

Cited by 4 | Viewed by 1375

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal multisystem disease characterized by progressive death of motor neurons, loss of muscle mass, and impaired energy metabolism. More than 40 genes are now known to be associated with ALS, which together account for the majority of familial forms of ALS and only 10% of sporadic ALS cases. To date, there is no consensus on the pathogenesis of ALS, which makes it difficult to develop effective therapy. Accumulating evidence indicates that mitochondria, which play an important role in cellular homeostasis, are the earliest targets in ALS, and abnormalities in their structure and functions contribute to the development of bioenergetic stress and disease progression. Mitochondria are known to be highly dynamic organelles, and their stability is maintained through a number of key regulatory pathways. Mitochondrial homeostasis is dynamically regulated via mitochondrial biogenesis, clearance, fission/fusion, and trafficking; however, the processes providing “quality control” and distribution of the organelles are prone to dysregulation in ALS. Here, we systematically summarized changes in mitochondrial turnover, dynamics, calcium homeostasis, and alterations in mitochondrial transport and functions to provide in-depth insights into disease progression pathways, which may have a significant impact on current symptomatic therapies and personalized treatment programs for patients with ALS. Full article

(This article belongs to the Special Issue Primary Mitochondrial Diseases and Secondary Mitochondrial Dysfunction: New Insights and Therapies)

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