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Frontiers in Bioscience (Landmark... Sep 2023Prohibitin-2 (PHB2) is a conserved protein in mitochondria that regulates various biological processes, including cell cycle, proliferation, apoptosis, transcription,... (Review)
Review
Prohibitin-2 (PHB2) is a conserved protein in mitochondria that regulates various biological processes, including cell cycle, proliferation, apoptosis, transcription, signal transduction, and mitochondrial ridge morphogenesis. Recently, there has been growing interest in the biological function of PHB2. This article primarily discusses the recent advances in the role of PHB2 in diseases.
Topics: Prohibitins; Mitochondria; Signal Transduction
PubMed: 37796696
DOI: 10.31083/j.fbl2809211 -
Cellular and Molecular Life Sciences :... Aug 2023Lipids in cell membranes and subcellular compartments play essential roles in numerous cellular processes, such as energy production, cell signaling and inflammation. A... (Review)
Review
Lipids in cell membranes and subcellular compartments play essential roles in numerous cellular processes, such as energy production, cell signaling and inflammation. A specific organelle lipidome is characterized by lipid synthesis and metabolism, intracellular trafficking, and lipid homeostasis in the organelle. Over the years, considerable effort has been directed to the identification of the lipid fingerprints of cellular organelles. However, these fingerprints are not fully characterized due to the large variety and structural complexity of lipids and the great variability in the abundance of different lipid species. The process becomes even more challenging when considering that the lipidome differs in health and disease contexts. This review summarizes the information available on the lipid composition of mammalian cell organelles, particularly the lipidome of the nucleus, mitochondrion, endoplasmic reticulum, Golgi apparatus, plasma membrane and organelles in the endocytic pathway. The lipid compositions of extracellular vesicles and lamellar bodies are also described. In addition, several examples of subcellular lipidome dynamics under physiological and pathological conditions are presented. Finally, challenges in mapping organelle lipidomes are discussed.
Topics: Animals; Lipids; Lipidomics; Lipid Metabolism; Organelles; Cell Nucleus; Mitochondria; Mammals
PubMed: 37530856
DOI: 10.1007/s00018-023-04889-3 -
Cellular Signalling Sep 2023Traditionally, mitochondria are known as "the powerhouse of the cell," responsible for energy (ATP) generation (by the electron transport chain, oxidative...
Traditionally, mitochondria are known as "the powerhouse of the cell," responsible for energy (ATP) generation (by the electron transport chain, oxidative phosphorylation, the tricarboxylic acid cycle, and fatty acid ß-oxidation), and for the regulation of several metabolic processes, including redox homeostasis, calcium signalling, and cellular apoptosis. The extensive studies conducted in the last decades portray mitochondria as multifaceted signalling organelles that ultimately command cells' survival or death. Based on current knowledge, we'll outline the mitochondrial signalling to other intracellular compartments in homeostasis and pathology-related mitochondrial stress conditions here. The following topics are discussed: (i) oxidative stress and mtROS signalling in mitohormesis, (ii) mitochondrial Ca signalling; (iii) the anterograde (nucleus-to-mitochondria) and retrograde (mitochondria-to-nucleus) signal transduction, (iv) the mtDNA role in immunity and inflammation, (v) the induction of mitophagy- and apoptosis - signalling cascades, (vi) the mitochondrial dysfunctions (mitochondriopathies) in cardiovascular, neurodegenerative, and malignant diseases. The novel insights into molecular mechanisms of mitochondria-mediated signalling can explain mitochondria adaptation to metabolic and environmental stresses to achieve cell survival.
Topics: Mitochondria; Oxidative Stress; Signal Transduction; Oxidation-Reduction; DNA, Mitochondrial
PubMed: 37422005
DOI: 10.1016/j.cellsig.2023.110794 -
Drug Discovery Today Jun 2024Mitochondria are one of the major sources of energy as well as regulators of cancer cell metabolism. Thus, they are potential targets for the effective treatment and... (Review)
Review
Mitochondria are one of the major sources of energy as well as regulators of cancer cell metabolism. Thus, they are potential targets for the effective treatment and management of cancer. Research has explored triphenylphosphonium (TPP) derivatives as potent cancer-targeting ligands because of their lipophilic nature and mitochondrial affinity. In this review, we summarize the utility of TPP-based conjugates targeting mitochondria in different types of cancer and other diseases, such as neurodegenerative and cardiovascular disorders. Such conjugates offer versatile therapeutic potential by modulating membrane potential, influencing reactive oxygen species (ROS) production, and coupling of molecular modifications (such as ATP metabolism and energy metabolism). Thus, we highlight TPP conjugates as promising mitochondria-targeting agents for use in targeted drug delivery systems.
Topics: Humans; Ligands; Organophosphorus Compounds; Drug Delivery Systems; Animals; Mitochondria; Neoplasms; Antineoplastic Agents; Reactive Oxygen Species
PubMed: 38641237
DOI: 10.1016/j.drudis.2024.103983 -
Life Sciences Nov 2023Circulating metabolites are indicators of systemic metabolic dysfunction and can be detected through contemporary techniques in metabolomics. These metabolites are... (Review)
Review
Circulating metabolites are indicators of systemic metabolic dysfunction and can be detected through contemporary techniques in metabolomics. These metabolites are involved in numerous mitochondrial metabolic processes including glycolysis, fatty acid β-oxidation, and amino acid catabolism, and changes in the abundance of these metabolites is implicated in the pathogenesis of cardiometabolic diseases (CMDs). Epigenetic regulation and direct metabolite-protein interactions modulate metabolism, both within cells and in the circulation. Dysfunction of multiple mitochondrial components stemming from mitochondrial DNA mutations are implicated in disease pathogenesis. This review will summarize the current state of knowledge regarding: i) the interactions between metabolites found within the mitochondrial environment during CMDs, ii) various metabolites' effects on cellular and systemic function, iii) how harnessing the power of metabolomic analyses represents the next frontier of precision medicine, and iv) how these concepts integrate to expand the clinical potential for translational cardiometabolic medicine.
Topics: Humans; Epigenesis, Genetic; Metabolomics; Metabolome; Mitochondria; Cardiovascular Diseases
PubMed: 37788764
DOI: 10.1016/j.lfs.2023.122137 -
Trends in Cell Biology Aug 2023Previous studies have shown that mitochondria play core roles in not only cancer stem cell (CSC) metabolism but also the regulation of CSC stemness maintenance and... (Review)
Review
Previous studies have shown that mitochondria play core roles in not only cancer stem cell (CSC) metabolism but also the regulation of CSC stemness maintenance and differentiation, which are key regulators of cancer progression and therapeutic resistance. Therefore, an in-depth study of the regulatory mechanism of mitochondria in CSCs is expected to provide a new target for cancer therapy. This article mainly introduces the roles played by mitochondria and related mechanisms in CSC stemness maintenance, metabolic transformation, and chemoresistance. The discussion mainly focuses on the following aspects: mitochondrial morphological structure, subcellular localization, mitochondrial DNA, mitochondrial metabolism, and mitophagy. The manuscript also describes the recent clinical research progress on mitochondria-targeted drugs and discusses the basic principles of their targeted strategies. Indeed, an understanding of the application of mitochondria in the regulation of CSCs will promote the development of novel CSC-targeted strategies, thereby significantly improving the long-term survival rate of patients with cancer.
Topics: Mitochondria; Neoplastic Stem Cells; Mitophagy; DNA, Mitochondrial; Drug Resistance, Neoplasm; Antineoplastic Agents; Neoplasms; Humans
PubMed: 37137792
DOI: 10.1016/j.tcb.2023.03.009 -
Aging Cell Dec 2023During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D...
During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.
Topics: Mice; Animals; Imaging, Three-Dimensional; Mitochondria Associated Membranes; Mitochondria; Mitochondrial Membranes; DNA, Mitochondrial; Mitochondrial Proteins; Mammals
PubMed: 37960952
DOI: 10.1111/acel.14009 -
Expert Review of Endocrinology &... Mar 2024Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney... (Review)
Review
INTRODUCTION
Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney dysfunction, and cancer. The current review explores the crucial role of mitochondria, essential for fuel metabolism, in diabetes-related processes.
AREAS COVERED
Mitochondrial deficits impact insulin-resistant skeletal muscles, adipose tissue, liver, and pancreatic β-cells, affecting glucose and lipid balance. Exercise emerges as a key factor in enhancing mitochondrial function, thereby reducing insulin resistance. Additionally, the therapeutic potential of mitochondrial uncoupling, which generates heat instead of ATP, is discussed. We explore the intricate link between mitochondrial function and diabetes, investigating genetic interventions to mitigate diabetes-related complications. We also cover the impact of insulin deficiency on mitochondrial function, the role of exercise in addressing mitochondrial defects in insulin resistance, and the potential of mitochondrial uncoupling. Furthermore, a comprehensive analysis of Mitochondrial Replacement Therapies (MRT) techniques is presented.
EXPERT OPINION
MRTs hold promise in preventing the transmission of mitochondrial disease. However, addressing ethical, regulatory, and technical considerations is crucial. Integrating mitochondrial-based treatments requires a careful balance between innovation and safety. Ethical dimensions and regulatory aspects of MRT are examined, emphasizing collaborative efforts for the responsible advancement of human health.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Mitochondria; Insulin; Glucose
PubMed: 38347803
DOI: 10.1080/17446651.2024.2307526 -
Mitochondrion May 2024Space is a challenging environment that deregulates individual homeostasis. The main external hazards associated with spaceflight include ionizing space radiation,... (Review)
Review
Space is a challenging environment that deregulates individual homeostasis. The main external hazards associated with spaceflight include ionizing space radiation, microgravity, isolation and confinement, distance from Earth, and hostile environment. Characterizing the biological responses to spaceflight environment is essential to validate the health risks, and to develop effective protection strategies. Mitochondria energetics is a key mechanism underpinning many physiological, ecological and evolutionary processes. Moreover, mitochondrial stress can be considered one of the fundamental features of space travel. So, we attempt to synthesize key information regarding the extensive effects of spaceflight on mitochondria. In summary, mitochondria are affected by all of the five main hazards of spaceflight at multiple levels, including their morphology, respiratory function, protein, and genetics, in various tissues and organ systems. We emphasize that investigating mitochondrial biology in spaceflight conditions should become the central focus of research on the impacts of spaceflight on human health, as this approach will help resolve numerous challenges of space health and combat several health disorders associated with mitochondrial dysfunction.
Topics: Space Flight; Humans; Mitochondria; Weightlessness; Stress, Physiological; Animals
PubMed: 38403094
DOI: 10.1016/j.mito.2024.101855 -
International Journal of Molecular... Jun 2024The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state... (Review)
Review
The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state of accelerated and premature aging. Aging kidney and CKD have numerous common characteristic features, ranging from pathological presentation and clinical manifestation to underlying mechanisms. The shared mechanisms underlying the process of kidney aging and the development of CKD include the increase in cellular senescence, the decrease in autophagy, mitochondrial dysfunction, and the alterations of epigenetic regulation, suggesting the existence of potential therapeutic targets that are applicable to both conditions. In this review, we provide a comprehensive overview of the common characteristics between aging kidney and CKD, encompassing morphological changes, functional alterations, and recent advancements in understanding the underlying mechanisms. Moreover, we discuss potential therapeutic strategies for targeting senescent cells in both the aging process and CKD.
Topics: Humans; Renal Insufficiency, Chronic; Aging; Cellular Senescence; Kidney; Animals; Epigenesis, Genetic; Mitochondria; Autophagy
PubMed: 38928291
DOI: 10.3390/ijms25126585