Mitochondrial Metabolism in Health and Disease: A Clinical Perspective

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1037

Special Issue Editors


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Department of Medical Sciences and Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: biochemistry; cell biology; molecular biology; metabolism; cancer
Special Issues, Collections and Topics in MDPI journals
1. Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine (Health Sciences Pole), University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
2. iCBR - Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine (Health Sciences Pole), University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
3. CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-507 Coimbra, Portugal
4. Institute for Interdisciplinary Research (IIIUC), Casa Costa Alemão - Pólo II, University of Coimbra, Rua D. Francisco de Lemos, 3030-789 Coimbra, Portugal
Interests: cell biology; health sciences; neurochemistry; (neuro)endocrinology; (neuro)pharmacology/(neuro)toxicology; (patho)physiology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Laboratory of Metabolism and Exercise (LaMetEx), Research Center in Physical Activity, health and Leisure (CIAFEL)-Faculty of Sports-University of Porto (FADEUP) and Laboratory for Integrative and Translational Research in Population Health (ITR), 4200-450 Porto, Portugal 2. CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC - Institute for Interdisciplinary Research, 3004-504 Coimbra, Portugal
Interests: Metabolism, cardiac mitochondria, Cardiovascular diseases, Developmental origins of health and disease (DOHaD), maternal and fetal health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since their likely endosymbiotic origin, mitochondria have been a major feature of eukaryotic cells. Their major mitochondrial functions include ATP production, mediated by the mitochondrial oxidative phosphorylation system, the triggering of apoptosis, encompassing the mitochondrial outer membrane permeabilization, and the regulation of calcium homeostasis through interactions with the endoplasmic reticulum. Mitochondria are also implicated in the production and detoxification of reactive oxygen species (ROS), being particularly susceptible to oxidative stress and major players in redox homeostasis. Mitochondria have their own genome and are highly dynamic organelles, undergoing fusion and fission, being involved in the regulation of innumerous cellular activities, including cell-cycle regulation, cell differentiation, cell proliferation, mitophagy, and autophagy. Due to the critical role of mitochondria in cell homeostasis and metabolism, mitochondrial dysfunctions can have a severe impact on the host, being involved in disorders including cancer and metabolic, cardiac, and neurodegenerative diseases.

In this Special Issue, we aim to collect a sample of the latest research in mitochondrial metabolism. Altogether, the articles published in this collection will reinforce the significance of this organelle in the functioning of the cell and in human diseases. We welcome original research and review manuscripts on any aspects of mitochondrial metabolism, including mitochondrial dynamics, mitochondrial genetics, bioenergetics, the intrinsic pathway of apoptosis, the regulation of calcium levels, and oxidative stress. Studies on mitochondrial dysfunction in human disorders, including cancer and metabolic, cardiac, and neurodegenerative diseases, are also welcome. As the mitochondrion is a common link among these fields, participating researchers may uncover broader implications to their findings.

Dr. Joao Pessoa
Dr. Ana I. Duarte
Dr. Susana P. Pereira
Guest Editors

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Keywords

  • mitochondrion
  • bioenergetics
  • oxidative stress
  • calcium homeostasis
  • apoptosis
  • cancer
  • metabolic diseases
  • cardiovascular diseases
  • neurodegenerative diseases

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Published Papers (1 paper)

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Review

29 pages, 3828 KiB  
Review
Pyruvate Kinase M1/2 Proteoformics for Accurate Insights into Energy Metabolism Abnormity to Promote the Overall Management of Ovarian Cancer Towards Predictive, Preventive, and Personalized Medicine Approaches
by Yan Wang, Nuo Xu, Marie Louise Ndzie Noah, Liang Chen and Xianquan Zhan
Metabolites 2025, 15(3), 203; https://doi.org/10.3390/metabo15030203 - 16 Mar 2025
Viewed by 636
Abstract
Ovarian cancer (OC) is a global health problem that frequently presents at advanced stages, is predisposed to recurrence, readily develops resistance to platinum-based drugs, and has a low survival rate. Predictive, preventive, and personalized medicine (PPPM/3PM) offers an integrated solution with the use [...] Read more.
Ovarian cancer (OC) is a global health problem that frequently presents at advanced stages, is predisposed to recurrence, readily develops resistance to platinum-based drugs, and has a low survival rate. Predictive, preventive, and personalized medicine (PPPM/3PM) offers an integrated solution with the use of genetic, proteomic, and metabolic biomarkers to identify high-risk individuals for early detection. Metabolic reprogramming is one of the key strategies employed by tumor cells to adapt to the microenvironment and support unlimited proliferation. Pyruvate kinases M1 and M2 (PKM1/2) are encoded by the PKM gene, a pivotal enzyme in the last step of the glycolytic pathway, which is at the crossroads of aerobic oxidation and the Warburg effect to serve as a potential regulator of glucose metabolism and influence cellular energy production and metabolic reprogramming. Commonly, the ratio of PKM1-to-PKM2 is changed in tumors compared to normal controls, and PKM2 is highly expressed in OC to induce a high glycolysis rate and participate in the malignant invasion and metastatic characteristics of cancer cells with epithelial/mesenchymal transition (EMT). PKM2 inhibitors suppress the migration and growth of OC cells by interfering with the Warburg effect. Proteoforms are the final structural and functional forms of a gene/protein, and the canonical protein PKM contains all proteoforms encoded by the same PKM gene. The complexity of PKM can be elucidated by proteoformics. The OC-specific PKM proteoform might represent a specific target for therapeutic interventions against OC. In the framework of PPPM/3PM, the OC-specific PKM proteoform might be the early warning and prognosis biomarker. It is important to clarify the molecular mechanisms of PKM proteoforms in cancer metabolism. This review analyzes the expression, function, and molecular mechanisms of PKM proteoforms in OC, which help identify specific biomarkers for OC. Full article
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