-
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 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 -
MBio Aug 2021Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium falciparum, are the cause of many important human and animal diseases. While T. gondii tachyzoites... (Review)
Review
Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium falciparum, are the cause of many important human and animal diseases. While T. gondii tachyzoites replicate through endodyogeny, during which two daughter cells are formed within the parental cell, P. falciparum replicates through schizogony, where up to 32 parasites are formed in a single infected red blood cell and even thousands of daughter cells during mosquito- or liver-stage development. These processes require a tightly orchestrated division and distribution over the daughter parasites of one-per-cell organelles such as the mitochondrion and apicoplast. Although proper organelle segregation is highly essential, the molecular mechanism and the key proteins involved remain largely unknown. In this review, we describe organelle dynamics during cell division in T. gondii and P. falciparum, summarize the current understanding of the molecular mechanisms underlying organelle fission in these parasites, and introduce candidate fission proteins.
Topics: Animals; Apicoplasts; Erythrocytes; Humans; Mitochondria; Parasites; Plasmodium falciparum; Protozoan Proteins; Toxoplasma
PubMed: 34425697
DOI: 10.1128/mBio.01409-21 -
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 -
Cellular and Molecular Life Sciences :... Dec 2016Cyclic adenosine 3, 5'-monophosphate (cAMP) is a ubiquitous second messenger regulating many biological processes, such as cell migration, differentiation, proliferation... (Review)
Review
Cyclic adenosine 3, 5'-monophosphate (cAMP) is a ubiquitous second messenger regulating many biological processes, such as cell migration, differentiation, proliferation and apoptosis. cAMP signaling functions not only on the plasma membrane, but also in the nucleus and in organelles such as mitochondria. Mitochondrial cAMP signaling is an indispensable part of the cytoplasm-mitochondrion crosstalk that maintains mitochondrial homeostasis, regulates mitochondrial dynamics, and modulates cellular stress responses and other signaling pathways. Recently, the compartmentalization of mitochondrial cAMP signaling has attracted great attentions. This new input should be carefully taken into account when we interpret the findings of mitochondrial cAMP signaling. In this review, we summarize previous and recent progress in our understanding of mitochondrial cAMP signaling, including the components of the signaling cascade, and the function and regulation of this signaling pathway in different mitochondrial compartments.
Topics: Animals; Cell Compartmentation; Cyclic AMP; Humans; Mitochondria; Models, Biological; Signal Transduction
PubMed: 27233501
DOI: 10.1007/s00018-016-2282-2 -
Life Sciences Jun 2023Aging is a natural process, characterized by progressive loss of physiological integrity, impaired function, and increased vulnerability to death. For centuries, people... (Review)
Review
Aging is a natural process, characterized by progressive loss of physiological integrity, impaired function, and increased vulnerability to death. For centuries, people have been trying hard to understand the process of aging and find effective ways to delay it. However, limited breakthroughs have been made in anti-aging area. Since the hallmarks of aging were summarized in 2013, increasing studies focus on the role of mitochondrial dysfunction in aging and aging-related degenerative diseases, such as neurodegenerative diseases, osteoarthritis, metabolic diseases, and cardiovascular diseases. Accumulating evidence indicates that restoring mitochondrial function and biogenesis exerts beneficial effects in extending lifespan and promoting healthy aging. In this paper, we provide an overview of mitochondrial changes during aging and summarize the advanced studies in mitochondrial therapies for the treatment of degenerative diseases. Current challenges and future perspectives are proposed to provide novel and promising directions for future research.
Topics: Humans; Aging; Mitochondria; Cardiovascular Diseases; Signal Transduction; Longevity
PubMed: 37030614
DOI: 10.1016/j.lfs.2023.121666 -
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 -
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