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British Journal of Cancer Jan 2021Although mitochondrial contributions to cancer have been recognised for approximately a century, given that mitochondrial DNA (mtDNA) is dwarfed by the size of the... (Review)
Review
Although mitochondrial contributions to cancer have been recognised for approximately a century, given that mitochondrial DNA (mtDNA) is dwarfed by the size of the nuclear genome (nDNA), nuclear genetics has represented a focal point in cancer biology, often at the expense of mtDNA and mitochondria. However, genomic sequencing and advances in in vivo models underscore the importance of mtDNA and mitochondria in cancer and metastasis. In this review, we explore the roles of mitochondria in the four defined 'hallmarks of metastasis': motility and invasion, microenvironment modulation, plasticity and colonisation. Biochemical processes within the mitochondria of both cancer cells and the stromal cells with which they interact are critical for each metastatic hallmark. We unravel complex dynamics in mitochondrial contributions to cancer, which are context-dependent and capable of either promoting metastasis or being leveraged to prevent it at various points of the metastatic cascade. Ultimately, mitochondrial contributions to cancer and metastasis are rooted in the capacity of these organelles to tune metabolic and genetic responses to dynamic microenvironmental cues.
Topics: Animals; Humans; Mitochondria; Neoplasm Invasiveness; Neoplasms; Tumor Microenvironment
PubMed: 33144695
DOI: 10.1038/s41416-020-01125-8 -
Cancer Treatment and Research... 2022Evidence supports the antitumoral effects of physical activity, either in experimental animal models or humans. However, the biological mechanisms by which physical... (Review)
Review
Evidence supports the antitumoral effects of physical activity, either in experimental animal models or humans. However, the biological mechanisms by which physical exercise modulates tumoral development are still unclear. An important feature of the tumor cells is the altered energy metabolism, often associated with definitions of tumor aggressiveness. Nevertheless, exercise can cause global metabolic changes in the body, as well as modulate tumor metabolism. Here we specifically discuss the metabolic changes found in tumors and how exercise can contribute to anti-tumoral effects by modulating the mitochondrial function, and tricarboxylic acid cycle-related metabolites of cancer cells. The effect of physical exercise on tumor metabolism is a new possibility for comprehension of cancer biology and developing therapies focused on tumor energy metabolism.
Topics: Animals; Citric Acid Cycle; Energy Metabolism; Exercise; Humans; Mitochondria; Neoplasms
PubMed: 35811248
DOI: 10.1016/j.ctarc.2022.100600 -
Mitochondrion Nov 2021Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS)... (Review)
Review
Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS) production and cell-free mitochondrial DNA (mtDNA) release, leading to increased inflammation. Mitophagy is a vital pathway, which selectively removes defective mitochondria through the process of autophagy. Thus, an impairment in the mitophagy pathway might trigger the gradual accumulation of defective mitochondria. Accumulating evidence suggest that inflammation and mitochondrial dysfunction are linked to the pathogenesis of depression. In this article, we have reviewed the role of impaired mitophagy as a contributing factor in depression pathophysiology. Further, we have discussed the potential therapeutic interventions aimed at modulating mitophagy in depression.
Topics: Depression; Humans; Mitochondria; Mitophagy
PubMed: 34478906
DOI: 10.1016/j.mito.2021.08.016 -
Mitochondrion Sep 2020Mitochondria are eukaryotic organelles known best for their roles in energy production and metabolism. While often thought of as simply the 'powerhouse of the cell,'... (Review)
Review
Mitochondria are eukaryotic organelles known best for their roles in energy production and metabolism. While often thought of as simply the 'powerhouse of the cell,' these organelles participate in a variety of critical cellular processes including reactive oxygen species (ROS) production, regulation of programmed cell death, modulation of inter- and intracellular nutrient signaling pathways, and maintenance of cellular proteostasis. Disrupted mitochondrial function is a hallmark of eukaryotic aging, and mitochondrial dysfunction has been reported to play a role in many aging-related diseases. While mitochondria are major players in human diseases, significant questions remain regarding their precise mechanistic role. In this review, we detail mechanisms by which mitochondrial dysfunction participate in disease and aging based on findings from model organisms and human genetics studies.
Topics: Aging; Apoptosis; Energy Metabolism; Humans; Mitochondria; Oxidative Stress; Proteostasis; Reactive Oxygen Species
PubMed: 32738358
DOI: 10.1016/j.mito.2020.07.007 -
The FEBS Journal Nov 2019Mitochondria are as highly specialized organelles and masters of the cellular energy metabolism in a constant and dynamic interplay with their cellular environment,... (Review)
Review
Mitochondria are as highly specialized organelles and masters of the cellular energy metabolism in a constant and dynamic interplay with their cellular environment, providing adenosine triphosphate, buffering Ca and fundamentally contributing to various signaling pathways. Hence, such broad field of action within eukaryotic cells requires a high level of structural and functional adaptation. Therefore, mitochondria are constantly moving and undergoing fusion and fission processes, changing their shape and their interaction with other organelles. Moreover, mitochondrial activity gets fine-tuned by intra- and interorganelle H , K , Na , and Ca signaling. In this review, we provide an up-to-date overview on mitochondrial strategies to adapt and respond to, as well as affect, their cellular environment. We also present cutting-edge technologies used to track and investigate subcellular signaling, essential to the understanding of various physiological and pathophysiological processes.
Topics: Animals; Energy Metabolism; Humans; Mitochondria; Mitochondrial Dynamics; Signal Transduction
PubMed: 31661602
DOI: 10.1111/febs.15103 -
Endocrinology Aug 2022Immune cells infiltrate adipose tissue as a function of age, sex, and diet, leading to a variety of regulatory processes linked to metabolic disease and dysfunction....
Immune cells infiltrate adipose tissue as a function of age, sex, and diet, leading to a variety of regulatory processes linked to metabolic disease and dysfunction. Cytokines and chemokines produced by resident macrophages, B cells, T cells and eosinophils play major role(s) in fat cell mitochondrial functions modulating pyruvate oxidation, electron transport and oxidative stress, branched chain amino acid metabolism, fatty acid oxidation, and apoptosis. Indeed, cytokine-dependent downregulation of numerous genes affecting mitochondrial metabolism is strongly linked to the development of the metabolic syndrome, whereas the potentiation of mitochondrial metabolism represents a counterregulatory process improving metabolic outcomes. In contrast, inflammatory cytokines activate mitochondrially linked cell death pathways such as apoptosis, pyroptosis, necroptosis, and ferroptosis. As such, the adipocyte mitochondrion represents a major intersection point for immunometabolic regulation of central metabolism.
Topics: Adipocytes; Adipose Tissue; Cytokines; Mitochondria; Oxidative Stress
PubMed: 35752995
DOI: 10.1210/endocr/bqac094 -
International Journal of Molecular... May 2022Mitochondria, traditionally identified as the powerhouses of eukaryotic cells, constitute a dynamic network of signaling platforms with multifaceted key roles in cell...
Mitochondria, traditionally identified as the powerhouses of eukaryotic cells, constitute a dynamic network of signaling platforms with multifaceted key roles in cell metabolism, proliferation and survival [...].
Topics: Energy Metabolism; Mitochondria; Signal Transduction
PubMed: 35628362
DOI: 10.3390/ijms23105552 -
International Journal of Molecular... Aug 2020Mitochondrial stress is considered as a factor that reprograms the mitochondrial biogenesis and metabolism. As known, SUMOylation occurs through a series of... (Review)
Review
Mitochondrial stress is considered as a factor that reprograms the mitochondrial biogenesis and metabolism. As known, SUMOylation occurs through a series of stress-induced biochemical reactions. During the process of SUMOylation, the small ubiquitin-like modifier (SUMO) and its specific proteases (SENPs) are key signal molecules. Furthermore, they are considered as novel mitochondrial stress sensors that respond to the signals produced by various stresses. The responses are critical for mitochondrial homeostasis. The scope of this review is to provide an overview of the function of SUMOylation in the mitochondrial stress response, to delineate a SUMOylation-involved signal network diagram, and to highlight a number of key questions that remain answered.
Topics: Animals; Caloric Restriction; Humans; Mitochondria; Organelle Biogenesis; Stress, Physiological; Sumoylation; Unfolded Protein Response
PubMed: 32781782
DOI: 10.3390/ijms21165657 -
International Journal of Molecular... Jul 2019Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic... (Review)
Review
Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.
Topics: Animals; Antineoplastic Agents; Cell Nucleus; Cisplatin; DNA, Mitochondrial; Drug Resistance, Neoplasm; Humans; Mitochondria; Mitochondrial Dynamics; Mitophagy; Neoplasms; Signal Transduction
PubMed: 31295873
DOI: 10.3390/ijms20143384 -
Cell Reports Dec 2022Nutrient availability regulates the C. elegans life cycle as well as mitochondrial physiology. Food deprivation significantly reduces mitochondrial genome (mtDNA)...
Nutrient availability regulates the C. elegans life cycle as well as mitochondrial physiology. Food deprivation significantly reduces mitochondrial genome (mtDNA) numbers and leads to aging-related phenotypes. Here we show that the bZIP (basic leucine zipper) protein ATFS-1, a mediator of the mitochondrial unfolded protein response (UPR), is required to promote growth and establish a functional germline after prolonged starvation. We find that recovery of mtDNA copy numbers and development after starvation requires mitochondrion-localized ATFS-1 but not its nuclear transcription activity. We also find that the insulin-like receptor DAF-2 functions upstream of ATFS-1 to modulate mtDNA content. We show that reducing DAF-2 activity represses ATFS-1 nuclear function while causing an increase in mtDNA content, partly mediated by mitochondrion-localized ATFS-1. Our data indicate the importance of the UPR in recovering mitochondrial mass and suggest that atfs-1-dependent mtDNA replication precedes mitochondrial network expansion after starvation.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Genome, Mitochondrial; DNA, Mitochondrial; Mitochondria; Unfolded Protein Response
PubMed: 36577367
DOI: 10.1016/j.celrep.2022.111875