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Biomolecules
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Advances in the Role of Mitochondria in Regulated Cell Death...
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Advances in the Role of Mitochondria in Regulated Cell Death Dysfunctions Associated with Human Pathologies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 7985

Special Issue Editors

Prof. Dr. Manuela Côrte-Real

E-Mail Website
Guest Editor
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal
Interests: regulated cell death; mitochondrial dysfunctions; cancer/yeast cells; anticancer/antifungal activities; lactoferrin
Special Issues, Collections and Topics in MDPI journals
Dr. Susana R. Chaves

E-Mail Website
Guest Editor
Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, Braga, Portugal
Interests: cell death; mitochondrial function; microbiology; molecular targets; cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Cátia Santos-Pereira

E-Mail Website
Guest Editor
1. Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal
2. Centre of Biological Engineering (CEB), Department of Biological Engineering, University of Minho, 4710-057 Braga, Portugal
3. LABBELS—Associate Laboratory, Braga/Guimaraes, Portugal
Interests: cell death; cancer; fungal infections; metagenomics; lactoferrin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Regulated cell death is an intricate and highly coordinated process involving a sequence of events that allows organisms to eliminate damaged, infected, or useless cells. When deregulated or inadequately executed, it compromises both the development and homeostasis of multicellular organisms and is thus associated with several human pathologies such as cancer and neurodegenerative diseases.

Mitochondria have often been attributed a central role in regulated cell death, especially in apoptotic cell death. In particular, a plethora of studies have shown that apoptosis can be pharmacologically modulated through the targeting of the mitochondrial outer membrane, which has great potential for therapeutic applications against different diseases. Mitochondria have also been implicated in the execution of non-apoptotic regulated cell death processes such as necroptosis, pyroptosis, ferroptosis, and mitochondrial permeability transition (MPT)-driven necrosis. However, how mitochondrial dysfunction in these processes is linked to diseases and which molecular components may be druggable is much less known. Filling this gap will therefore extend the potential of pharmacologically targeting mitochondria towards the modulation of these non-apoptotic subroutines and uncover novel opportunities for therapeutic strategies to overcome the cell death deregulation associated with human disorders.

In this Special Issue, we welcome submissions with new perspectives on roles of mitochondria in regulated cell death that are associated with Human pathologies and that can contribute to novel therapeutic interventions.

Prof. Dr. Manuela Côrte-Real
Dr. Susana R. Chaves
Dr. Cátia Santos-Pereira
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • regulated cell death (RCD)
  • mitochondrial dysfunctions
  • non-apoptotic RCD
  • human disorders

Published Papers (3 papers)

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13 pages, 1564 KiB  
Article
Enhancement of Acetate-Induced Apoptosis of Colorectal Cancer Cells by Cathepsin D Inhibition Depends on Oligomycin A-Sensitive Respiration
by Sara Alves, Cátia Santos-Pereira, Cláudia S. F. Oliveira, Ana Preto, Susana R. Chaves and Manuela Côrte-Real
Biomolecules 2024, 14(4), 473; https://doi.org/10.3390/biom14040473 - 12 Apr 2024
Viewed by 330
Abstract
Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest [...] Read more.
Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors. Full article
(This article belongs to the Special Issue Advances in the Role of Mitochondria in Regulated Cell Death Dysfunctions Associated with Human Pathologies)
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Review

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27 pages, 2700 KiB  
Review
Mitochondrial Modulators: The Defender
by Emmanuel Makinde, Linlin Ma, George D. Mellick and Yunjiang Feng
Biomolecules 2023, 13(2), 226; https://doi.org/10.3390/biom13020226 - 24 Jan 2023
Cited by 7 | Viewed by 2911
Abstract
Mitochondria are widely considered the “power hub” of the cell because of their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond the production of ATP, which is the major source of chemical energy supply in eukaryotes, mitochondria are also central to [...] Read more.
Mitochondria are widely considered the “power hub” of the cell because of their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond the production of ATP, which is the major source of chemical energy supply in eukaryotes, mitochondria are also central to calcium homeostasis, reactive oxygen species (ROS) balance, and cell apoptosis. The mitochondria also perform crucial multifaceted roles in biosynthetic pathways, serving as an important source of building blocks for the biosynthesis of fatty acid, cholesterol, amino acid, glucose, and heme. Since mitochondria play multiple vital roles in the cell, it is not surprising that disruption of mitochondrial function has been linked to a myriad of diseases, including neurodegenerative diseases, cancer, and metabolic disorders. In this review, we discuss the key physiological and pathological functions of mitochondria and present bioactive compounds with protective effects on the mitochondria and their mechanisms of action. We highlight promising compounds and existing difficulties limiting the therapeutic use of these compounds and potential solutions. We also provide insights and perspectives into future research windows on mitochondrial modulators. Full article
(This article belongs to the Special Issue Advances in the Role of Mitochondria in Regulated Cell Death Dysfunctions Associated with Human Pathologies)
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15 pages, 1569 KiB  
Review
The Pathophysiological Significance of “Mitochondrial Ejection” from Cells
by Qintao Fan, Yasuhiro Maejima, Lai Wei, Shun Nakagama, Yuka Shiheido-Watanabe and Tetsuo Sasano
Biomolecules 2022, 12(12), 1770; https://doi.org/10.3390/biom12121770 - 28 Nov 2022
Cited by 2 | Viewed by 4148
Abstract
Mitochondria have beneficial effects on cells by producing ATP and contributing to various biosynthetic procedures. On the other hand, dysfunctional mitochondria have detrimental effects on cells by inducing cellular damage, inflammation, and causing apoptosis in response to various stimuli. Therefore, a series of [...] Read more.
Mitochondria have beneficial effects on cells by producing ATP and contributing to various biosynthetic procedures. On the other hand, dysfunctional mitochondria have detrimental effects on cells by inducing cellular damage, inflammation, and causing apoptosis in response to various stimuli. Therefore, a series of mitochondrial quality control pathways are required for the physiological state of cells to be maintained. Recent research has provided solid evidence to support that mitochondria are ejected from cells for transcellular degradation or transferred to other cells as metabolic support or regulatory messengers. In this review, we summarize the current understanding of the regulation of mitochondrial transmigration across the plasma membranes and discuss the functional significance of this unexpected phenomenon, with an additional focus on the impact on the pathogenesis of cardiovascular diseases. We also provide some perspective concerning the unrevealed mechanisms underlying mitochondrial ejection as well as existing problems and challenges concerning the therapeutic application of mitochondrial ejection. Full article
(This article belongs to the Special Issue Advances in the Role of Mitochondria in Regulated Cell Death Dysfunctions Associated with Human Pathologies)
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