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Journal of Biochemistry Feb 2024The cytoplasm of eukaryotes is dynamically zoned by membrane-bound and membraneless organelles. Cytoplasmic zoning allows various biochemical reactions to take place at... (Review)
Review
The cytoplasm of eukaryotes is dynamically zoned by membrane-bound and membraneless organelles. Cytoplasmic zoning allows various biochemical reactions to take place at the right time and place. Mitochondrion is a membrane-bound organelle that provides a zone for intracellular energy production and metabolism of lipids and iron. A key feature of mitochondria is their high dynamics: mitochondria constantly undergo fusion and fission, and excess or damaged mitochondria are selectively eliminated by mitophagy. Therefore, mitochondria are appropriate model systems to understand dynamic cytoplasmic zoning by membrane organelles. In this review, we summarize the molecular mechanisms of mitochondrial fusion and fission as well as mitophagy unveiled through studies using yeast and mammalian models.
Topics: Animals; Mitochondria; Mitophagy; Saccharomyces cerevisiae; Mitochondrial Dynamics; Mammals
PubMed: 38016932
DOI: 10.1093/jb/mvad098 -
Methods in Enzymology 2020The mitochondrion performs critical roles in eukaryotic cells including ATP production, cell growth, survival, apoptosis, and differentiation. Many human diseases can be...
The mitochondrion performs critical roles in eukaryotic cells including ATP production, cell growth, survival, apoptosis, and differentiation. Many human diseases can be traced to dysfunction within the mitochondria, but selective delivery of therapeutics into the mitochondria has been challenging. This chapter describes the detailed protocols for the synthesis of a new family of mitochondrion-targeting, cell-penetrating molecules (CPMs) and their application for the delivery of small-molecule and peptidyl cargos into the mitochondrial matrix. Live-cell confocal microscopic imaging of HeLa cells treated with a variety of CPM-cargo conjugates revealed that the CPMs efficiently and specifically deliver membrane-impermeable linear and cyclic peptidyl cargos into the mitochondrial matrix, as long as the cargo carries no more than two negative charges.
Topics: Apoptosis; Drug Delivery Systems; HeLa Cells; Humans; Microscopy, Confocal; Mitochondria
PubMed: 32713527
DOI: 10.1016/bs.mie.2020.04.044 -
The FEBS Journal Nov 2022Molecular oxygen possesses a dual nature due to its highly reactive free radical property: it is capable of oxidizing metabolic substrates to generate cellular energy,... (Review)
Review
Molecular oxygen possesses a dual nature due to its highly reactive free radical property: it is capable of oxidizing metabolic substrates to generate cellular energy, but can also serve as a substrate for genotoxic reactive oxygen species generation. As a labile substance upon which aerobic life depends, the mechanisms for handling cellular oxygen have been fine-tuned and orchestrated in evolution. Protection from atmospheric oxygen toxicity as originally posited by the Endosymbiotic Theory of the Mitochondrion is likely to be one basic principle underlying oxygen homeostasis. We briefly review the literature on oxygen homeostasis both in vitro and in vivo with a focus on the role of the mitochondrion where the majority of cellular oxygen is consumed. The insights gleaned from these basic mechanisms are likely to be important for understanding disease pathogenesis and developing strategies for maintaining health.
Topics: Mitochondria; Free Radicals; Oxygen; Homeostasis; Reactive Oxygen Species; Oxidative Stress
PubMed: 34235856
DOI: 10.1111/febs.16115 -
The FEBS Journal Nov 2022With the development of advanced technologies, many small open reading frames (sORFs) have been found to be translated into micropeptides. Interestingly, a considerable... (Review)
Review
With the development of advanced technologies, many small open reading frames (sORFs) have been found to be translated into micropeptides. Interestingly, a considerable proportion of micropeptides are located in mitochondria, which are designated here as mitochondrion-located peptides (MLPs). These MLPs often contain a transmembrane domain and show a high degree of conservation across species. They usually act as co-factors of large proteins and play regulatory roles in mitochondria such as electron transport in the respiratory chain, reactive oxygen species (ROS) production, metabolic homeostasis, and so on. Deficiency of MLPs disturbs diverse physiological processes including immunity, differentiation, and metabolism both in vivo and in vitro. These findings reveal crucial functions for MLPs and provide fresh insights into diverse mitochondrion-associated biological processes and diseases.
Topics: Open Reading Frames; Peptides; Mitochondria
PubMed: 35599630
DOI: 10.1111/febs.16532 -
Mitochondrion Sep 2023Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging.... (Review)
Review
Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35%-60% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation.
Topics: Animals; Mice; Selenium; Mitochondria; Epilepsy; Seizures; Iron
PubMed: 37582467
DOI: 10.1016/j.mito.2023.08.002 -
Mitochondrion May 2020Plant mitochondrial genomes are renowned for their structural complexity, extreme variation in size and mutation rates, and ability to incorporate foreign DNA. Parasitic... (Review)
Review
Plant mitochondrial genomes are renowned for their structural complexity, extreme variation in size and mutation rates, and ability to incorporate foreign DNA. Parasitic flowering plants are no exception, and the close association between parasite and host may even enhance the likelihood of horizontal gene transfer (HGT) between them. Recent studies on mistletoes (Viscum) have revealed that these parasites have lost an exceptional number of mitochondrial genes, including all complex I genes of the respiratory chain. At the same time, an altered respiratory pathway has been demonstrated. Here we review the current understanding of mitochondrial evolution in parasitic plants with a special emphasis on HGT to and from parasite mitochondrial genomes, as well as the uniquely altered mitochondria in Viscum and related plants.
Topics: Evolution, Molecular; Gene Transfer, Horizontal; Genetic Variation; Genome, Mitochondrial; Magnoliopsida; Mitochondria; Phylogeny
PubMed: 32224234
DOI: 10.1016/j.mito.2020.03.008 -
Current Pediatric Reviews 2023Mitochondria are highly-dynamic, membrane-bound organelles that generate most of the chemical energy needed to power the biochemical reactions in eukaryotic cells. These... (Review)
Review
Mitochondria are highly-dynamic, membrane-bound organelles that generate most of the chemical energy needed to power the biochemical reactions in eukaryotic cells. These organelles also communicate with the nucleus and other cellular structures to help maintain somatic homeostasis, allow cellular adaptation to stress, and help maintain the developmental trajectory. Mitochondria also perform numerous other functions to support metabolic, energetic, and epigenetic regulation in our cells. There is increasing information on various disorders caused by defects in intrinsic mitochondrial or supporting nuclear genes, on different organ systems. In this review, we have summarized the ultrastructural morphology, structural components, our current understanding of the evolution, biogenesis, dynamics, function, clinical manifestations of mitochondrial dysfunction, and future possibilities. The implications of deficits in mitochondrial dynamics and signaling for embryo viability and offspring health are also explored. We present information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus.
Topics: Humans; Epigenesis, Genetic; Mitochondria; Signal Transduction
PubMed: 36545736
DOI: 10.2174/1573396319666221221110728 -
Biochimica Et Biophysica Acta.... Feb 2021The mitochondrion is often referred as the cellular powerhouse because the organelle oxidizes organic acids and NADH derived from nutriments, converting around 40% of... (Review)
Review
The mitochondrion is often referred as the cellular powerhouse because the organelle oxidizes organic acids and NADH derived from nutriments, converting around 40% of the Gibbs free energy change of these reactions into ATP, the major energy currency of cell metabolism. Mitochondria are thus microscopic furnaces that inevitably release heat as a by-product of these reactions, and this contributes to body warming, especially in endotherms like birds and mammals. Over the last decade, the idea has emerged that mitochondria could be warmer than the cytosol, because of their intense energy metabolism. It has even been suggested that our own mitochondria could operate under normal conditions at a temperature close to 50 °C, something difficult to reconcile with the laws of thermal physics. Here, using our combined expertise in biology and physics, we exhaustively review the reports that led to the concept of a hot mitochondrion, which is essentially based on the development and use of a variety of molecular thermosensors whose intrinsic fluorescence is modified by temperature. Then, we discuss the physical concepts of heat diffusion, including mechanisms like phonons scattering, which occur in the nanoscale range. Although most of approaches with thermosensors studies present relatively sparse data and lack absolute temperature calibration, overall, they do support the hypothesis of hot mitochondria. However, there is no convincing physical explanation that would allow the organelle to maintain a higher temperature than its surroundings. We nevertheless proposed some research directions, mainly biological, that might help throw light on this intriguing conundrum.
Topics: Animals; Energy Metabolism; Humans; Mitochondria
PubMed: 33248118
DOI: 10.1016/j.bbabio.2020.148348 -
Mitochondrion Nov 2019Spatiotemporal changes in the abundance, shape, and cellular localization of the mitochondrial network, also known as mitochondrial dynamics, are now widely recognized... (Review)
Review
Spatiotemporal changes in the abundance, shape, and cellular localization of the mitochondrial network, also known as mitochondrial dynamics, are now widely recognized to play a key role in mitochondrial and cellular physiology as well as disease states. This process involves coordinated remodeling of the outer and inner mitochondrial membranes by conserved dynamin-like guanosine triphosphatases and their partner molecules in response to various physiological and stress stimuli. Although the core machineries that mediate fusion and partitioning of the mitochondrial network have been extensively characterized, many aspects of their function and regulation are incompletely understood and only beginning to emerge. In the present review we briefly summarize current knowledge about how the key mitochondrial dynamics-mediating factors are regulated via selective proteolysis by mitochondrial and cellular proteolytic machineries.
Topics: Animals; Mitochondria; Mitochondrial Dynamics; Mitochondrial Membranes; Mitochondrial Proteins; Proteolysis
PubMed: 31029640
DOI: 10.1016/j.mito.2019.04.008 -
Viruses Dec 2023Mitochondria have been identified as the "powerhouse" of the cell, generating the cellular energy, ATP, for almost seven decades. Research over time has uncovered a... (Review)
Review
Mitochondria have been identified as the "powerhouse" of the cell, generating the cellular energy, ATP, for almost seven decades. Research over time has uncovered a multifaceted role of the mitochondrion in processes such as cellular stress signaling, generating precursor molecules, immune response, and apoptosis to name a few. Dysfunctional mitochondria resulting from a departure in homeostasis results in cellular degeneration. Viruses hijack host cell machinery to facilitate their own replication in the absence of a bonafide replication machinery. Replication being an energy intensive process necessitates regulation of the host cell oxidative phosphorylation occurring at the electron transport chain in the mitochondria to generate energy. Mitochondria, therefore, can be an attractive therapeutic target by limiting energy for viral replication. In this review we focus on the physiology of oxidative phosphorylation and on the limited studies highlighting the regulatory effects viruses induce on the electron transport chain.
Topics: Humans; Oxidative Phosphorylation; Mitochondria; Apoptosis; Signal Transduction; Virus Diseases; Phosphorylation; Oxidative Stress
PubMed: 38140621
DOI: 10.3390/v15122380