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American Journal of Physiology. Cell... Dec 2006
Topics: DNA, Mitochondrial; Humans; Mitochondria; Models, Biological; Oxidative Phosphorylation; Systems Biology
PubMed: 17102034
DOI: 10.1152/ajpcell.00481.2006 -
Mitochondrion May 2022Mitochondrial transplantation involves the replacement or augmentation of native mitochondria damaged, by ischemia, with viable, respiration-competent mitochondria... (Review)
Review
Mitochondrial transplantation involves the replacement or augmentation of native mitochondria damaged, by ischemia, with viable, respiration-competent mitochondria isolated from non-ischemic tissue obtained from the patient's own body. The uptake and cellular functional integration of the transplanted mitochondria appears to occur in all cell types. Efficacy and safety have been demonstrated in cell culture, isolated perfused organ, in vivo large animal studies and in a first-human clinical study. Herein, we review our findings and provide insight for use in the treatment of organ ischemia- reperfusion injury.
Topics: Animals; Cell Culture Techniques; Mitochondria; Mitochondria, Heart; Reperfusion Injury
PubMed: 35217248
DOI: 10.1016/j.mito.2022.02.007 -
Cold Spring Harbor Perspectives in... Sep 2012Viewed through the lens of the genome it contains, the mitochondrion is of unquestioned bacterial ancestry, originating from within the bacterial phylum... (Review)
Review
Viewed through the lens of the genome it contains, the mitochondrion is of unquestioned bacterial ancestry, originating from within the bacterial phylum α-Proteobacteria (Alphaproteobacteria). Accordingly, the endosymbiont hypothesis--the idea that the mitochondrion evolved from a bacterial progenitor via symbiosis within an essentially eukaryotic host cell--has assumed the status of a theory. Yet mitochondrial genome evolution has taken radically different pathways in diverse eukaryotic lineages, and the organelle itself is increasingly viewed as a genetic and functional mosaic, with the bulk of the mitochondrial proteome having an evolutionary origin outside Alphaproteobacteria. New data continue to reshape our views regarding mitochondrial evolution, particularly raising the question of whether the mitochondrion originated after the eukaryotic cell arose, as assumed in the classical endosymbiont hypothesis, or whether this organelle had its beginning at the same time as the cell containing it.
Topics: Biological Evolution; Evolution, Molecular; Genome, Mitochondrial; Mitochondria; Models, Biological; Phylogeny; Proteome; Symbiosis
PubMed: 22952398
DOI: 10.1101/cshperspect.a011403 -
Angewandte Chemie (International Ed. in... Dec 2018Mitochondrial dysfunction is linked to a variety of human illnesses, but selective delivery of therapeutics into the mitochondrion is challenging. Now a family of...
Mitochondrial dysfunction is linked to a variety of human illnesses, but selective delivery of therapeutics into the mitochondrion is challenging. Now a family of amphipathic cell-penetrating motifs (CPMs) is presented, consisting of four guanidinium groups and one or two aromatic hydrophobic groups (naphthalene) assembled through a central scaffold (a benzene ring). The CPMs and CPM-cargo conjugates efficiently enter the interior of cultured mammalian cells and are specifically localized into the mitochondrial matrix, as revealed by high-resolution confocal microscopy. With a membrane-impermeable peptide as cargo, the CPMs exhibited ≥170-fold higher delivery efficiency than previous mitochondrial delivery vehicles. Conjugation of a small-molecule inhibitor of heat shock protein 90 to a CPM resulted in accumulation of the inhibitor inside the mitochondrial matrix with greatly enhanced anticancer activity. The CPMs showed minimal effect on the viability or the mitochondrial membrane potential of mammalian cells.
Topics: Cell Survival; Cell-Penetrating Peptides; Drug Delivery Systems; HeLa Cells; Humans; Membrane Potential, Mitochondrial; Mitochondria; Molecular Structure
PubMed: 30376611
DOI: 10.1002/anie.201811940 -
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 -
Mitochondrion Nov 2014Cytoplasmic male sterility and its fertility restoration via nuclear genes offer the possibility to understand the role of mitochondria during microsporogenesis. In most...
Cytoplasmic male sterility and its fertility restoration via nuclear genes offer the possibility to understand the role of mitochondria during microsporogenesis. In most cases rearrangements in the mitochondrial DNA involving known mitochondrial genes as well as unknown sequences result in the creation of new chimeric open reading frames, which encode proteins containing transmembrane domains. So far, most of the CMS systems have been characterized via restriction fragment polymorphisms followed by transcript analysis. However, whole mitochondrial genome sequence analyses comparing male sterile and fertile cytoplasm open options for deeper insights into mitochondrial genome rearrangements. We more and more start to unravel how mitochondria are involved in triggering death of the male reproductive organs. Reduced levels of ATP accompanied by increased concentrations of reactive oxygen species, which are produced more under conditions of mitochondrial dysfunction, seem to play a major role in the fate of pollen production. Nuclear genes, so called restorer-of-fertility are able to restore the male fertility. Fertility restoration can occur via pentatricopeptide repeat (PPR) proteins or via different mechanisms involving non-PPR proteins.
Topics: DNA, Mitochondrial; Fertility; Gametogenesis, Plant; Gene Rearrangement; Genes, Mitochondrial; Genome, Mitochondrial; Mitochondria; Plant Physiological Phenomena; Plants
PubMed: 24732436
DOI: 10.1016/j.mito.2014.04.004 -
Mitochondrion Mar 2020
Topics: Energy Metabolism; Homeostasis; Humans; Mitochondria; Mitochondrial Diseases
PubMed: 31917323
DOI: 10.1016/j.mito.2019.12.007 -
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 2023Allotopic expression is the functional transfer of an organellar gene to the nucleus, followed by synthesis of the gene product in the cytosol and import into the... (Review)
Review
Allotopic expression is the functional transfer of an organellar gene to the nucleus, followed by synthesis of the gene product in the cytosol and import into the appropriate organellar sub compartment. Here, we focus on mitochondrial genes encoding OXPHOS subunits that were naturally transferred to the nucleus, and critically review experimental evidence that claim their allotopic expression. We emphasize aspects that may have been overlooked before, i.e., when modifying a mitochondrial gene for allotopic expression━besides adapting the codon usage and including sequences encoding mitochondrial targeting signals━three additional constraints should be considered: (i) the average apparent free energy of membrane insertion (μΔG) of the transmembrane stretches (TMS) in proteins earmarked for the inner mitochondrial membrane, (ii) the final, functional topology attained by each membrane-bound OXPHOS subunit; and (iii) the defined mechanism by which the protein translocator TIM23 sorts cytosol-synthesized precursors. The mechanistic constraints imposed by TIM23 dictate the operation of two pathways through which alpha-helices in TMS are sorted, that eventually determine the final topology of membrane proteins. We used the biological hydrophobicity scale to assign an average apparent free energy of membrane insertion (μΔG) and a "traffic light" color code to all TMS of OXPHOS membrane proteins, thereby predicting which are more likely to be internalized into mitochondria if allotopically produced. We propose that the design of proteins for allotopic expression must make allowance for μΔG maximization of highly hydrophobic TMS in polypeptides whose corresponding genes have not been transferred to the nucleus in some organisms.
Topics: Mitochondria; Mitochondrial Membranes; Membrane Proteins; Genes, Mitochondrial; Protein Transport; Saccharomyces cerevisiae Proteins
PubMed: 37739243
DOI: 10.1016/j.mito.2023.09.004