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Cells Mar 2020The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is... (Review)
Review
The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver's physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.
Topics: Animals; Humans; Liver; Liver Diseases; Mitochondria; Mitophagy; Receptors, Cell Surface; Signal Transduction
PubMed: 32244304
DOI: 10.3390/cells9040837 -
Hepatology (Baltimore, Md.) May 2003
Review
Topics: Animals; Hepatocytes; Humans; Liver Diseases; Mitochondria
PubMed: 12717408
DOI: 10.1002/hep.510370541 -
Current Neuropharmacology 2020Atherosclerosis is a chronic inflammatory condition that affects different arteries in the human body and often leads to severe neurological complications, such as... (Review)
Review
Mitochondrion as a Selective Target for the Treatment of Atherosclerosis: Role of Mitochondrial DNA Mutations and Defective Mitophagy in the Pathogenesis of Atherosclerosis and Chronic Inflammation.
BACKGROUND
Atherosclerosis is a chronic inflammatory condition that affects different arteries in the human body and often leads to severe neurological complications, such as stroke and its sequelae. Affected blood vessels develop atherosclerotic lesions in the form of focal thickening of the intimal layer, so called atherosclerotic plaques.
OBJECTIVES
Despite the high priority of atherosclerosis research for global health and the numerous preclinical and clinical studies conducted, currently, there is no effective pharmacological treatment that directly impacts atherosclerotic plaques. Many knowledge gaps exist in our understanding of the mechanisms of plaque formation. In this review, we discuss the role of mitochondria in different cell types involved in atherogenesis and provide information about mtDNA mutations associated with the disease.
RESULTS
Mitochondria of blood and arterial wall cells appear to be one of the important factors in disease initiation and development. Significant experimental evidence connects oxidative stress associated with mitochondrial dysfunction and vascular disease. Moreover, mitochondrial DNA (mtDNA) deletions and mutations are being considered as potential disease markers. Further study of mtDNA damage and associated dysfunction may open new perspectives for atherosclerosis treatment.
CONCLUSION
Mitochondria can be considered as important disease-modifying factors in several chronic pathologies. Deletions and mutations of mtDNA may be used as potential disease markers. Mitochondria-targeting antioxidant therapies appear to be promising for the development of treatment of atherosclerosis and other diseases associated with oxidative stress and chronic inflammation.
Topics: Animals; Atherosclerosis; Cholesterol, LDL; DNA, Mitochondrial; Humans; Inflammation; Mitochondria; Mitophagy; Muscle, Smooth, Vascular; Mutation; Oxidative Stress; Plaque, Atherosclerotic
PubMed: 31744449
DOI: 10.2174/1570159X17666191118125018 -
International Review of Cytology 2005The mitochondrion is generally considered to be a defining feature of eukaryotic cells, yet most anaerobic eukaryotes lack this organelle. Many of these were previously... (Review)
Review
The mitochondrion is generally considered to be a defining feature of eukaryotic cells, yet most anaerobic eukaryotes lack this organelle. Many of these were previously thought to derive from eukaryotes that diverged prior to acquisition of the organelle through endosymbiosis. It is now known that all extant eukaryotes are descended from an ancestor that had a mitochondrion and that in anaerobic eukaryotes the organelle has been modified into either hydrogenosomes, which continue to generate energy for the host cell, or mitosomes, which do not. These organelles have each arisen independently several times. Recent evidence suggests a shared derived characteristic that may be responsible for the retention of the organelles in the absence of the better-known mitochondrial functions--iron-sulfur cluster assembly. This review explores the events leading to this new understanding of mitochondrion-derived organelles in amitochondriate eukaryotes, the current state of our knowledge, and future areas for investigation.
Topics: Animals; Eukaryota; Fungi; Mitochondria; Organelles
PubMed: 16157181
DOI: 10.1016/S0074-7696(05)44005-X -
Lancet (London, England) May 2012Mitochondria have a crucial role in cellular bioenergetics and apoptosis, and thus are important to support cell function and in determination of cell death pathways.... (Review)
Review
Mitochondria have a crucial role in cellular bioenergetics and apoptosis, and thus are important to support cell function and in determination of cell death pathways. Inherited mitochondrial diseases can be caused by mutations of mitochondrial DNA or of nuclear genes that encode mitochondrial proteins. Although many mitochondrial disorders are multisystemic, some are tissue specific--eg, optic neuropathy, sensorineural deafness, and type 2 diabetes mellitus. In the past few years, several disorders have been associated with mutations of nuclear genes responsible for mitochondrial DNA maintenance and function, and the potential contribution of mitochondrial abnormalities to progressive neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease has been recognised. The process of mitochondrial fission-fusion has become a focus of attention in human disease. Importantly, the mitochondrion is now a target for therapeutic interventions that encompass small molecules, transcriptional regulation, and genetic manipulation, offering opportunities to treat a diverse range of diseases.
Topics: Apoptosis; Disease Progression; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Mutation
PubMed: 22482939
DOI: 10.1016/S0140-6736(11)61305-6 -
Progress in Lipid Research Oct 2013A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are... (Review)
Review
A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol. Other mitochondrial membrane lipids such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sterols and sphingolipids have to be imported. The mitochondrial lipid composition, the biosynthesis and the import of mitochondrial lipids as well as the regulation of these processes will be main issues of this review article. Furthermore, interactions of lipids and mitochondrial proteins which are highly important for various mitochondrial processes will be discussed. Malfunction or loss of enzymes involved in mitochondrial phospholipid biosynthesis lead to dysfunction of cell respiration, affect the assembly and stability of the mitochondrial protein import machinery and cause abnormal mitochondrial morphology or even lethality. Molecular aspects of these processes as well as diseases related to defects in the formation of mitochondrial membranes will be described.
Topics: Lipids; Mitochondria; Mitochondrial Membranes; Plants; Saccharomyces cerevisiae
PubMed: 24007978
DOI: 10.1016/j.plipres.2013.07.002 -
BioEssays : News and Reviews in... Sep 2019The mitochondrion is known as the "powerhouse" of eukaryotic cells since it is the main site of adenosine 5'-triphosphate (ATP) production. Using a temperature-sensitive... (Review)
Review
The mitochondrion is known as the "powerhouse" of eukaryotic cells since it is the main site of adenosine 5'-triphosphate (ATP) production. Using a temperature-sensitive fluorescent probe, it has recently been suggested that the stray free energy, not captured into ATP, is potentially sufficient to sustain mitochondrial temperatures higher than the cellular environment, possibly reaching up to 50 °C. By 50 °C, some DNA and mitochondrial proteins may reach their melting temperatures; how then do these biomolecules maintain their structure and function? Further, the production of reactive oxygen species (ROS) accelerates with temperature, implying higher oxidative stresses in the mitochondrion than generally appreciated. Herein, it is proposed that mitochondrial heat shock proteins (particularly Hsp70), in addition to their roles in protein transport and folding, protect mitochondrial proteins and DNA from thermal and ROS damage. Other thermoprotectant mechanisms are also discussed.
Topics: DNA, Mitochondrial; Heat-Shock Proteins; Mitochondria; Mitochondrial Proteins; Reactive Oxygen Species; Symbiosis; Temperature; Up-Regulation
PubMed: 31379014
DOI: 10.1002/bies.201900055 -
Biochimie May 2014The mitochondria have arisen as a consequence of endosymbiosis of an ancestral α-proteobacterium with a methane-producing archae. The main function of the canonical... (Review)
Review
The mitochondria have arisen as a consequence of endosymbiosis of an ancestral α-proteobacterium with a methane-producing archae. The main function of the canonical aerobic mitochondria include ATP generation via oxidative phosphorylation, heme and phospholipid synthesis, calcium homeostasis, programmed cell death, and the formation of iron-sulfur clusters. Under oxygen-restricted conditions, the mitochondrion has often undergone remarkable reductive alterations of its content and function, leading to the generation of mitochondrion-related organelles (MROs), such as mitosomes, hydrogenosomes, and mithochondrion-like organelles, which are found in a wide range of anaerobic/microaerophilic eukaryotes that include several medically important parasitic protists such as Entamoeba histolytica, Giardia intestinalis, Trichomonas vaginalis, Cryptosporidium parvum, Blastocystis hominis, and Encephalitozoon cuniculi, as well as free-living protists such as Sawyeria marylandensis, Neocallimastix patriciarum, and Mastigamoeba balamuthi. The transformation from canonical aerobic mitochondria to MROs apparently have occurred in independent lineages, and resulted in the diversity of their components and functions. Due to medical and veterinary importance of the MRO-possessing human- and animal-pathogenic protozoa, their genomic, transcriptomic, proteomic, and biochemical evidence has been accumulated. Detailed analyses of the constituents and functions of the MROs in such anaerobic pathogenic protozoa, which reside oxygen-deprived or oxygen-poor environments such as the mammalian intestine and the genital organs, should illuminate the current evolutionary status of the MROs in these organisms, and give insight to environmental constraints that drive the evolution of eukaryotes and their organelles. In this review, we summarize and discuss the diverse metabolic functions and protein transport systems of the MROs from anaerobic parasitic protozoa.
Topics: Alveolata; Amoebozoa; Anaerobiosis; Biodiversity; Biological Evolution; Cryptophyta; Diplomonadida; Gene Expression Regulation; Genome, Mitochondrial; Humans; Mitochondria; Mitochondrial Proteins; Neocallimastix; Phylogeny; Protein Transport
PubMed: 24316280
DOI: 10.1016/j.biochi.2013.11.018 -
Mitochondrion Jul 2018
Topics: Animals; Energy Metabolism; Humans; Immunity, Innate; Mitochondria; Mitochondrial Dynamics; Periodicals as Topic; Signal Transduction
PubMed: 29887010
DOI: 10.1016/j.mito.2018.05.002 -
Mitochondrion Nov 2019Mitochondrial dynamics shape the mitochondrial network and contribute to mitochondrial function and quality control. Mitochondrial fusion and division are integrated... (Review)
Review
Mitochondrial dynamics shape the mitochondrial network and contribute to mitochondrial function and quality control. Mitochondrial fusion and division are integrated into diverse cellular functions and respond to changes in cell physiology. Imbalanced mitochondrial dynamics are associated with a range of diseases that are broadly characterized by impaired mitochondrial function and increased cell death. In various disease models, modulating mitochondrial fusion and division with either small molecules or genetic approaches has improved function. Although additional mechanistic understanding of mitochondrial fusion and division will be critical to inform further therapeutic approaches, mitochondrial dynamics represent a powerful therapeutic target in a wide range of human diseases.
Topics: Animals; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Dynamics
PubMed: 31228566
DOI: 10.1016/j.mito.2019.06.002