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Cellular and Molecular Biology of Mitochondria in Human Health and Diseases

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

Deadline for manuscript submissions: 30 November 2024 | Viewed by 4973

Special Issue Editor


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Guest Editor
Department of Regenerative Medicine, Kyoto Prefectural University of Medicine, 465 Kajii cho, Kamigyo ku, Kyoto 602-8655, Japan
Interests: mitochondrial biology; lysosomal biology; organelle; RNA decay; gene therapy
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Special Issue Information

Dear Colleagues,

Apart from being energy-producing plants, mitochondria regulate cell differentiation, play a major role in the initiation and progression of cancer, are responsible for cell death, serve as a command post for immunity, contribute to the maintenance of body temperature, play a key role in the external environment and intrinsic stress responses, and are so deeply involved in the aging process that they can be said to be involved in every process. The two life forms, which began in symbiosis, make up a single, brilliantly integrated organism. However, from time to time, we can glimpse the selfish behavior of the little one in the dysfunction of disease, and we know that it has a vigorous survival strategy. Biology has long been described by information reduced to genes encoded in the nucleus and has not given much significance to the malfunction of mitochondria, which were originally a separate life form. Recent advances in mitochondrial biology have revealed a series of events in which mitochondrial function responds to instructions from the nuclear genome, leading to alterations in the phenotype. In this special issue, we would like to provide an editorial on the understanding of diseases with pathologies based on mitochondrial dysfunction and the potential of new therapeutic strategies by correcting mitochondrial function. It would be a great pleasure for the editors to highlight the possibility of a common approach of restoring mitochondrial function to diseases with completely different etiologies, such as cancer, infectious diseases, neurodegenerative diseases, autoimmune diseases, and diabetes, by providing a cross-sectional overview from the perspective of mitochondria.

Leading by Prof. Dr. Satoshi Gojo and assisting by our Topical Advisory Panel Member Dr. Małgorzata Blatkiewicz (Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland), we sincerely hope to receive papers from researchers focusing on mitochondria in a variety of fields.

Prof. Dr. Satoshi Gojo
Guest Editor

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Keywords

  • mitochondria
  • mitophagy
  • oxidative phosphorylation
  • apoptosis
  • integrated stress response
  • heteroplasmy
  • calcium dynamics
  • reactive oxygen species
  • fusion/fission
  • mitochondrial quality control

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Published Papers (3 papers)

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Research

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17 pages, 2836 KiB  
Article
Identification of Antioxidant Methyl Derivatives of Ortho-Carbonyl Hydroquinones That Reduce Caco-2 Cell Energetic Metabolism and Alpha-Glucosidase Activity
by Matías Monroy-Cárdenas, Cristopher Almarza, Paulina Valenzuela-Hormazábal, David Ramírez, Félix A. Urra, Maximiliano Martínez-Cifuentes and Ramiro Araya-Maturana
Int. J. Mol. Sci. 2024, 25(15), 8334; https://doi.org/10.3390/ijms25158334 - 30 Jul 2024
Viewed by 997
Abstract
α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, [...] Read more.
α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds’ effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome. Full article
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15 pages, 3250 KiB  
Article
Berberine Induces Mitophagy through Adenosine Monophosphate-Activated Protein Kinase and Ameliorates Mitochondrial Dysfunction in PINK1 Knockout Mouse Embryonic Fibroblasts
by Jee-Hyun Um, Kang-Min Lee, Young-Yeon Kim, Da-Ye Lee, Eunmi Kim, Dong-Hyun Kim and Jeanho Yun
Int. J. Mol. Sci. 2024, 25(1), 219; https://doi.org/10.3390/ijms25010219 - 22 Dec 2023
Cited by 5 | Viewed by 2120
Abstract
Mitophagy stimulation has been shown to have a therapeutic effect on various neurodegenerative diseases. However, nontoxic mitophagy inducers are still very limited. In this study, we found that the natural alkaloid berberine exhibited mitophagy stimulation activity in various human cells. Berberine did not [...] Read more.
Mitophagy stimulation has been shown to have a therapeutic effect on various neurodegenerative diseases. However, nontoxic mitophagy inducers are still very limited. In this study, we found that the natural alkaloid berberine exhibited mitophagy stimulation activity in various human cells. Berberine did not interfere with mitochondrial function, unlike the well-known mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and subsequently induced mitochondrial biogenesis. Berberine treatment induced the activation of adenosine monophosphate-activated protein kinase (AMPK), and the AMPK inhibitor compound C abolished berberine-induced mitophagy, suggesting that AMPK activation is essential for berberine-induced mitophagy. Notably, berberine treatment reversed mitochondrial dysfunction in PINK1 knockout mouse embryonic fibroblasts. Our results suggest that berberine is a mitophagy-specific inducer and can be used as a therapeutic treatment for neurodegenerative diseases, including Parkinson’s disease, and that natural alkaloids are potential sources of mitophagy inducers. Full article
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Review

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12 pages, 273 KiB  
Review
Cellular and Molecular Biology of Mitochondria in Chronic Obstructive Pulmonary Disease
by Chin-Ling Li and Shih-Feng Liu
Int. J. Mol. Sci. 2024, 25(14), 7780; https://doi.org/10.3390/ijms25147780 - 16 Jul 2024
Viewed by 1243
Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by enduring airflow limitation and chronic inflammation. Growing evidence highlights mitochondrial dysfunction as a critical factor in COPD development and progression. This review explores the cellular and molecular biology of mitochondria in [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by enduring airflow limitation and chronic inflammation. Growing evidence highlights mitochondrial dysfunction as a critical factor in COPD development and progression. This review explores the cellular and molecular biology of mitochondria in COPD, focusing on structural and functional changes, including alterations in mitochondrial shape, behavior, and respiratory chain complexes. We discuss the impact on cellular signaling pathways, apoptosis, and cellular aging. Therapeutic strategies targeting mitochondrial dysfunction, such as antioxidants and mitochondrial biogenesis inducers, are examined for their potential to manage COPD. Additionally, we consider the role of mitochondrial biomarkers in diagnosis, evaluating disease progression, and monitoring treatment efficacy. Understanding the interplay between mitochondrial biology and COPD is crucial for developing targeted therapies to slow disease progression and improve patient outcomes. Despite advances, further research is needed to fully elucidate mitochondrial dysfunction mechanisms, discover new biomarkers, and develop targeted therapies, aiming for comprehensive disease management that preserves lung function and enhances the quality of life for COPD patients. Full article
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