-
Current Opinion in Genetics &... Jun 2016Diabetes is increasingly prevalent and a primary contributor to the major causes of disability and death. Despite the central role of mitochondria in metabolism, the... (Review)
Review
Diabetes is increasingly prevalent and a primary contributor to the major causes of disability and death. Despite the central role of mitochondria in metabolism, the relationship between mitochondrial quality and insulin action remains unclear. An increasing number of genetically-engineered and aging rodent models are shedding additional light on the mitochondrion's role in regulating glucose metabolism and insulin sensitivity by modulating mitochondrial morphology, function and quality control pathways. Clarification of the role of mitochondria in regulating key cellular processes including metabolic flux, autophagy, and apoptosis will drive the development of novel therapeutic strategies for maintaining mitochondrial quality and improving human health.
Topics: Animals; Apoptosis; Autophagy; Diabetes Mellitus; Humans; Insulin Resistance; Mice; Mitochondria; Rats
PubMed: 27318536
DOI: 10.1016/j.gde.2016.05.007 -
Central Nervous System Agents in... Sep 2009Chaperones are proteins that assist the correct folding of other protein clients either when the clients are being synthesized or at their functional localities.... (Review)
Review
Chaperones are proteins that assist the correct folding of other protein clients either when the clients are being synthesized or at their functional localities. Chaperones are responsible for certain diseases. The sigma-1 receptor is recently identified as a receptor chaperone whose activity can be activated/deactivated by specific ligands. Under physiological conditions, the sigma-1 receptor chaperones the functional IP3 receptor at the endoplasmic reticulum and mitochondrion interface to ensure proper Ca(2+) signaling from endoplasmic reticulum into mitochondrion. However, under pathological conditions whereby cells encounter enormous stress that results in the endoplasmic reticulum losing its global Ca(2+) homeostasis, the sigma-1 receptor translocates and counteracts the arising apoptosis. Thus, the sigma-1 receptor is a receptor chaperone essential for the metabotropic receptor signaling and for the survival against cellular stress. The sigma-1 receptor has been implicated in many diseases including addiction, pain, depression, stroke, and cancer. Whether the chaperone activity of the sigma-1 receptor attributes to those diseases awaits further investigation.
Topics: Animals; Calcium Signaling; Endoplasmic Reticulum; Humans; Inositol 1,4,5-Trisphosphate Receptors; Ligands; Mitochondria; Molecular Chaperones; Receptors, sigma; Signal Transduction; Sigma-1 Receptor
PubMed: 20021352
DOI: 10.2174/1871524910909030184 -
Frontiers in Bioscience (Scholar... Jan 2013The genetic contribution is one of the most notable factors that play a main role in the risk of OA. Despite the genetics of this disease is complex and the finding of... (Review)
Review
The genetic contribution is one of the most notable factors that play a main role in the risk of OA. Despite the genetics of this disease is complex and the finding of risk-related genes has been very challenging, evidence for genetic predisposition has been reported. Besides, in the last years recent evidences indicate that the mitochondrion is implicated in OA. In this context, the mtDNA haplogroups, defined as individual groups characterized by the presence of a particular set of single nucleotide polymorphisms (SNPs) in the mtDNA sequence, emerged as new genetic variants involved in this pathology. Moreover, it has been described that mtDNA damage not only accumulates in OA chondrocytes, but also that OA chondrocytes have limited mtDNA repair capacity. In this review we will focus on the influence of mitochondrial genetics and the mtDNA haplogroups in the prevalence, severity and progression of the OA disease, as well as their incidence on many OA-related features, such as serum levels of OA-related molecular markers, Nitric Oxide production or telomere length.
Topics: DNA, Mitochondrial; Genetic Predisposition to Disease; Humans; Mitochondria; Osteoarthritis
PubMed: 23277056
DOI: 10.2741/s377 -
The Journal of Eukaryotic Microbiology Nov 2022Toxoplasma gondii is a member of the apicomplexan phylum, a group of single-celled eukaryotic parasites that cause significant human morbidity and mortality around the... (Review)
Review
Toxoplasma gondii is a member of the apicomplexan phylum, a group of single-celled eukaryotic parasites that cause significant human morbidity and mortality around the world. T. gondii harbors two organelles of endosymbiotic origin: a non-photosynthetic plastid, known as the apicoplast, and a single mitochondrion derived from the ancient engulfment of an α-proteobacterium. Due to excitement surrounding the novelty of the apicoplast, the T. gondii mitochondrion was, to a certain extent, overlooked for about two decades. However, recent work has illustrated that the mitochondrion is an essential hub of apicomplexan-specific biology. Development of novel techniques, such as cryo-electron microscopy, complexome profiling, and next-generation sequencing have led to a renaissance in mitochondrial studies. This review will cover what is currently known about key features of the T. gondii mitochondrion, ranging from its genome to protein import machinery and biochemical pathways. Particular focus will be given to mitochondrial features that diverge significantly from the mammalian host, along with discussion of this important organelle as a drug target.
Topics: Animals; Humans; Toxoplasma; Parasites; Cryoelectron Microscopy; Apicoplasts; Mitochondria; Mammals
PubMed: 35315174
DOI: 10.1111/jeu.12906 -
American Journal of Physiology. Cell... Dec 2006The mitochondrion represents a unique opportunity to apply mathematical modeling to a complex biological system. Understanding mitochondrial function and control is... (Review)
Review
The mitochondrion represents a unique opportunity to apply mathematical modeling to a complex biological system. Understanding mitochondrial function and control is important since this organelle is critical in energy metabolism as well as playing key roles in biochemical synthesis, redox control/signaling, and apoptosis. A mathematical model, or hypothesis, provides several useful insights including a rigorous test of the consensus view of the operation of a biological process as well as providing methods of testing and creating new hypotheses. The advantages of the mitochondrial system for applying a mathematical model include the relative simplicity and understanding of the matrix reactions, the ability to study the mitochondria as a independent contained organelle, and, most importantly, one can dynamically measure many of the internal reaction intermediates, on line. The developing ability to internally monitor events within the metabolic network, rather than just the inflow and outflow, is extremely useful in creating critical bounds on complex mathematical models using the individual reaction mechanisms available. However, many serious problems remain in creating a working model of mitochondrial function including the incomplete definition of metabolic pathways, the uncertainty of using in vitro enzyme kinetics, as well as regulatory data in the intact system and the unknown chemical activities of relevant molecules in the matrix. Despite these formidable limitations, the advantages of the mitochondrial system make it one of the best defined mammalian metabolic networks that can be used as a model system for understanding the application and use of mathematical models to study biological systems.
Topics: Animals; Mathematics; Mitochondria; Mitochondrial Proteins; Models, Biological; Oxidation-Reduction; Oxidative Phosphorylation
PubMed: 16971500
DOI: 10.1152/ajpcell.00223.2006 -
Journal of Cell Science Nov 2022The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed...
The single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitochondrion membrane and the parasite pellicle. The outer mitochondrial membrane-associated protein LMF1 is critical for the correct positioning of the mitochondrion. Intracellular parasites lacking LMF1 fail to form the lasso-shaped mitochondrion. To identify other proteins that tether the mitochondrion of the parasite to the pellicle, we performed a yeast two-hybrid screen for LMF1 interactors. We identified 70 putative interactors localized in different cellular compartments, such as the apical end of the parasite, mitochondrial membrane and the inner membrane complex (IMC), including with the pellicle protein IMC10. Using protein-protein interaction assays, we confirmed the interaction of LMF1 with IMC10. Conditional knockdown of IMC10 does not affect parasite viability but severely affects mitochondrial morphology in intracellular parasites and mitochondrial distribution to the daughter cells during division. In effect, IMC10 knockdown phenocopies disruption of LMF1, suggesting that these two proteins define a novel membrane tether between the mitochondrion and the IMC in Toxoplasma. This article has an associated First Person interview with the first author of the paper.
Topics: Animals; Membrane Proteins; Mitochondria; Mitochondrial Membranes; Parasites; Protozoan Proteins; Toxoplasma
PubMed: 36314270
DOI: 10.1242/jcs.260083 -
Cold Spring Harbor Perspectives in... Jul 2014Comparative genomics has revealed that the last eukaryotic common ancestor possessed the hallmark cellular architecture of modern eukaryotes. However, the remarkable... (Review)
Review
Comparative genomics has revealed that the last eukaryotic common ancestor possessed the hallmark cellular architecture of modern eukaryotes. However, the remarkable success of such analyses has created a dilemma. If key eukaryotic features are ancestral to this group, then establishing the relative timing of their origins becomes difficult. In discussions of eukaryote origins, special significance has been placed on the timing of mitochondrial acquisition. In one view, mitochondrial acquisition was the trigger for eukaryogenesis. Others argue that development of phagocytosis was a prerequisite to acquisition. Results from comparative genomics and molecular phylogeny are often invoked to support one or the other scenario. We show here that the associations between specific cell biological models of eukaryogenesis and evolutionary genomic data are not as strong as many suppose. Disentangling these eliminates many of the arguments that polarize current debate.
Topics: Biological Evolution; Eukaryota; Mitochondria; Models, Biological; Phagocytosis; Phylogeny; Symbiosis
PubMed: 25038049
DOI: 10.1101/cshperspect.a015990 -
Mitochondrion Nov 2014Higher plant mitochondrial genomes exhibit much greater structural complexity compared to most other organisms. Unlike well-characterized metazoan mitochondrial DNA... (Review)
Review
Higher plant mitochondrial genomes exhibit much greater structural complexity compared to most other organisms. Unlike well-characterized metazoan mitochondrial DNA (mtDNA) replication, an understanding of the mechanism(s) and proteins involved in plant mtDNA replication remains unclear. Several plant mtDNA replication proteins, including DNA polymerases, DNA primase/helicase, and accessory proteins have been identified. Mitochondrial dynamics, genome structure, and the complexity of dual-targeted and dual-function proteins that provide at least partial redundancy suggest that plants have a unique model for maintaining and replicating mtDNA when compared to the replication mechanism utilized by most metazoan organisms.
Topics: DNA Replication; Mitochondria; Mitochondrial Proteins; Plant Proteins; Plants
PubMed: 24681310
DOI: 10.1016/j.mito.2014.03.008 -
Cells Sep 2021Emerging evidence suggests that mitochondrion-endoplasmic reticulum (ER) and mitochondrion-lipid droplet (LD) contact sites are critical in regulating lipid metabolism... (Review)
Review
Emerging evidence suggests that mitochondrion-endoplasmic reticulum (ER) and mitochondrion-lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion-ER and mitochondrion-LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion-LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.
Topics: Alcohol-Related Disorders; Animals; Endoplasmic Reticulum; Hepatocytes; Humans; Lipid Droplets; Lipid Metabolism; Mitochondria; Non-alcoholic Fatty Liver Disease
PubMed: 34571924
DOI: 10.3390/cells10092273 -
Mitochondrion Jun 2010The cellular process of macromolecular degradation known as macroautophagy has long been known to play a role in the elimination of mitochondria. Over the past decade,... (Review)
Review
The cellular process of macromolecular degradation known as macroautophagy has long been known to play a role in the elimination of mitochondria. Over the past decade, much progress has been made in the development of systems by which the nature and mechanism of mitochondria degradation may be studied. Recent findings imply that the degradation of mitochondria via autophagy may be more specific and more tightly regulated than originally thought, and have led to designation of this specific type of autophagy as "mitophagy". In this review we provide a brief history of the development of mitophagy models and their associated discoveries.
Topics: Animals; Autophagy; Fungi; Mammals; Mitochondria
PubMed: 20083234
DOI: 10.1016/j.mito.2010.01.005