-
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 -
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 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 -
CNS Neuroscience & Therapeutics Jul 2019The mitochondrion is a unique organelle with a diverse range of functions. Mitochondrial dysfunction is a key pathological process in several neurodegenerative diseases.... (Review)
Review
The mitochondrion is a unique organelle with a diverse range of functions. Mitochondrial dysfunction is a key pathological process in several neurodegenerative diseases. Mitochondria are mostly important for energy production; however, they also have roles in Ca homeostasis, ROS production, and apoptosis. There are two major systems in place, which regulate mitochondrial integrity, mitochondrial dynamics, and mitophagy. These two processes remove damaged mitochondria from cells and protect the functional mitochondrial population. These quality control systems often become dysfunctional during neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, causing mitochondrial dysfunction and severe neurological symptoms.
Topics: Animals; Humans; Mitochondria; Neurodegenerative Diseases
PubMed: 30746905
DOI: 10.1111/cns.13105 -
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 -
Journal of Neuroscience Research Oct 2017Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in... (Review)
Review
Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in mitochondrial dynamic imbalance, free radical production, calcium accumulation, intrinsic cell death pathway activation and eventually cell death. Therefore, preserving or promoting mitochondrial function is a potential therapeutic target for the treatment of neurodegenerative disorders. Mitochondrial biogenesis is a process by which new mitochondria are produced from existing mitochondria. This biogenesis process is regulated by Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1alpha (PGC-1α). Once being activated by either phosphorylation or de-acetylation, PGC-1α activates nuclear respiratory factor 1 and 2 (NRF1 and NRF2), and subsequently mitochondrial transcription factor A (Tfam). The activation of this PGC-1α - NRF -Tfam pathway leads to synthesis of mitochondrial DNA and proteins and generation of new mitochondria. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Humans; Mitochondria; Nerve Degeneration; Organelle Biogenesis
PubMed: 28301064
DOI: 10.1002/jnr.24042 -
Cellular and Molecular Life Sciences :... Nov 2017The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis... (Review)
Review
The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors. Moreover, they attenuate the pathological processes including carcinogenesis and other hyperproliferative/inflammatory conditions. Interestingly, mitochondria appear to be a central hub of melatonin metabolism in the skin cells. Furthermore, substantial evidence has accumulated on the protective role of the melatonin against ultraviolet radiation and the attendant mitochondrial dysfunction. Melatonin and its metabolites appear to have a modulatory impact on mitochondrion redox and bioenergetic homeostasis, as well as the anti-apoptotic effects. Of note, some metabolites exhibit even greater impact than melatonin alone. Herein, we emphasize that melatonin-mitochondria axis would control integumental functions designed to protect local and perhaps global homeostasis. Given the phylogenetic origin and primordial actions of melatonin, we propose that the melatonin-related mitochondrial functions represent an evolutionary conserved mechanism involved in cellular adaptive response to skin injury and repair.
Topics: Animals; Antioxidants; Humans; Melatonin; Mitochondria; Skin; Skin Physiological Phenomena
PubMed: 28803347
DOI: 10.1007/s00018-017-2617-7