scholarly journals Physiological and pathological roles of mitochondrial SLC25 carriers

2013 ◽  
Vol 454 (3) ◽  
pp. 371-386 ◽  
Author(s):  
Manuel Gutiérrez-Aguilar ◽  
Christopher P. Baines
Keyword(s):  
Mitochondrial Membrane ◽  
Current Knowledge ◽  
Transmembrane Helix ◽  
Building Blocks ◽  
Proper Function ◽  
Inner Mitochondrial Membrane ◽  
Health And Disease ◽  
Metabolic Reactions ◽  
Solute Carrier

The mitochondrion relies on compartmentalization of certain enzymes, ions and metabolites for the sake of efficient metabolism. In order to fulfil its activities, a myriad of carriers are properly expressed, targeted and folded in the inner mitochondrial membrane. Among these carriers, the six-transmembrane-helix mitochondrial SLC25 (solute carrier family 25) proteins facilitate transport of solutes with disparate chemical identities across the inner mitochondrial membrane. Although their proper function replenishes building blocks needed for metabolic reactions, dysfunctional SLC25 proteins are involved in pathological states. It is the purpose of the present review to cover the current knowledge on the role of SLC25 transporters in health and disease.

scholarly journals Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 728 ◽  
Author(s):  
Giuseppe Paradies ◽  
Valeria Paradies ◽  
Francesca M. Ruggiero ◽  
Giuseppe Petrosillo
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Protein Import ◽  
Building Blocks ◽  
Inner Mitochondrial Membrane ◽  
Atp Production ◽  
Membrane Morphology ◽  
Transport Chain ◽  
Health And Disease

In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that are vital for cell survival. Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction.

The human cortical autonomic network and volitional exercise in health and disease

2018 ◽  
Vol 43 (11) ◽  
pp. 1122-1130 ◽  
Author(s):  
Baraa K. Al-Khazraji ◽  
J. Kevin Shoemaker
Keyword(s):  
Current Knowledge ◽  
Insular Cortex ◽  
Cardiovascular Control ◽  
Anterior Cingulate ◽  
Disease States ◽  
Autonomic Activation ◽  
Imaging Research ◽  
Health And Disease ◽  
Cortical Regions

The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain’s higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the “cortical autonomic network” (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.

The Salivary miRNome: A Promising Biomarker of Disease

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Tomei ◽  
Harshitha Shobha Manjunath ◽  
Selvasankar Murugesan ◽  
Souhaila Al Khodor
Keyword(s):  
Current Knowledge ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Circulating Mirnas ◽  
Disease Pathogenesis ◽  
Technical Aspects ◽  
Recent Developments ◽  
Health And Disease ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids, and hence can serve as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling and highlighting the applicability of miRNA screening to clinical practice.

scholarly journals The Gut Ecosystem: A Critical Player in Stroke

2020 ◽  
Author(s):  
Rosa Delgado Jiménez ◽  
Corinne Benakis
Keyword(s):  
Current Knowledge ◽  
Critical Factor ◽  
Intestinal Microbiome ◽  
Brain Disorders ◽  
Therapeutic Approaches ◽  
Health And Disease ◽  
Brain Stroke ◽  
The Brain ◽  
Improve Patient

AbstractThe intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

Mitochondrial Ca2+ Buffering Regulates Synaptic Transmission Between Retinal Amacrine Cells

2002 ◽  
Vol 87 (3) ◽  
pp. 1426-1439 ◽  
Author(s):  
Kathryn Medler ◽  
Evanna L. Gleason
Keyword(s):  
Synaptic Transmission ◽  
Mitochondrial Membrane ◽  
Amacrine Cell ◽  
Critical Role ◽  
Amacrine Cells ◽  
Normal Function ◽  
Inner Mitochondrial Membrane ◽  
Physiological Properties ◽  
Low Levels

The diverse functions of retinal amacrine cells are reliant on the physiological properties of their synapses. Here we examine the role of mitochondria as Ca2+ buffering organelles in synaptic transmission between GABAergic amacrine cells. We used the protonophore p-trifluoromethoxy-phenylhydrazone (FCCP) to dissipate the membrane potential across the inner mitochondrial membrane that normally sustains the activity of the mitochondrial Ca2+ uniporter. Measurements of cytosolic Ca2+ levels reveal that prolonged depolarization-induced Ca2+ elevations measured at the cell body are altered by inhibition of mitochondrial Ca2+ uptake. Furthermore, an analysis of the ratio of Ca2+ efflux on the plasma membrane Na-Ca exchanger to influx through Ca2+ channels during voltage steps indicates that mitochondria can also buffer Ca2+ loads induced by relatively brief stimuli. Importantly, we also demonstrate that mitochondrial Ca2+ uptake operates at rest to help maintain low cytosolic Ca2+ levels. This aspect of mitochondrial Ca2+ buffering suggests that in amacrine cells, the normal function of Ca2+-dependent mechanisms would be contingent upon ongoing mitochondrial Ca2+ uptake. To test the role of mitochondrial Ca2+ buffering at amacrine cell synapses, we record from amacrine cells receiving GABAergic synaptic input. The Ca2+ elevations produced by inhibition of mitochondrial Ca2+uptake are localized and sufficient in magnitude to stimulate exocytosis, indicating that mitochondria help to maintain low levels of exocytosis at rest. However, we found that inhibition of mitochondrial Ca2+ uptake during evoked synaptic transmission results in a reduction in the charge transferred at the synapse. Recordings from isolated amacrine cells reveal that this is most likely due to the increase in the inactivation of presynaptic Ca2+ channels observed in the absence of mitochondrial Ca2+ buffering. These results demonstrate that mitochondrial Ca2+ buffering plays a critical role in the function of amacrine cell synapses.

scholarly journals Keeping α-Synuclein at Bay: A More Active Role of Molecular Chaperones in Preventing Mitochondrial Interactions and Transition to Pathological States?

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 289
Author(s):  
Emelie E. Aspholm ◽  
Irena Matečko-Burmann ◽  
Björn M. Burmann
Keyword(s):  
Molecular Chaperones ◽  
Mitochondrial Membrane ◽  
Structural Transition ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Protein Aggregates ◽  
Active Role ◽  
Proteolytic Processing ◽  
Membrane Disruption

The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation of Lewy bodies, intracellular inclusions containing protein aggregates as well as broken organelles found in the brains of Parkinson’s patients. In parallel, a short motif around Tyr39 was identified as being crucial for the aggregation of α-synuclein. Interestingly, this region is also one of the main segments in contact with a diverse pool of molecular chaperones. Further, it could be shown that the inhibition of the chaperone:α-synuclein interaction leads to a binding of α-synuclein to mitochondria, which could also be shown to lead to mitochondrial membrane disruption as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases. Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading to enhanced mitochondrial interaction and consequential mitochondrial breakage, which might mark the initial stages of the structural transition of α-synuclein towards its pathological states.

scholarly journals In Vitro Import of a Nuclearly Encoded tRNA into the Mitochondrion of Trypanosoma brucei

1999 ◽  
Vol 19 (9) ◽  
pp. 6253-6259 ◽  
Author(s):  
Audra E. Yermovsky-Kammerer ◽  
Stephen L. Hajduk
Keyword(s):  
Membrane Potential ◽  
Trypanosoma Brucei ◽  
Mitochondrial Membrane ◽  
Protein Component ◽  
Proper Function ◽  
Mitochondrial Rna ◽  
Inner Mitochondrial Membrane ◽  
Trna Import ◽  
Trna Substrate

ABSTRACT All of the mitochondrial tRNAs of Trypanosoma bruceihave been shown to be encoded in the nucleus and must be imported into the mitochondrion. The import of nuclearly encoded tRNAs into the mitochondrion has been demonstrated in a variety of organisms and is essential for proper function in the mitochondrion. An in vitro import assay has been developed to study the pathway of tRNA import inT. brucei. The in vitro system utilizes crude isolated trypanosome mitochondria and synthetic RNAs transcribed from a cloned nucleus-encoded tRNA gene cluster. The substrate, composed of tRNASer and tRNALeu, is transcribed in tandem with a 59-nucleotide intergenic region. The tandem tRNA substrate is imported rapidly, while the mature-size tRNALeu fails to be imported in this system. These results suggest that the preferred substrate for tRNA import into trypanosome mitochondria is a precursor molecule composed of tandemly linked tRNAs. Import of the tandem tRNA substrate requires (i) a protein component that is associated with the surface of the mitochondrion, (ii) ATP pools both outside and within the mitochondrion, and (iii) a membrane potential. Dissipation of the proton gradient across the inner mitochondrial membrane by treatment with an uncoupling agent inhibits import of the tandem tRNA substrate. Characterization of the import requirements indicates that mitochondrial RNA import proceeds by a pathway including a protein component associated with the outer mitochondrial membrane, ATP-dependent steps, and a mitochondrial membrane potential.

Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants

1996 ◽  
Vol 29 (2) ◽  
pp. 169-202 ◽  
Author(s):  
Vladimir P. Skulachev
Keyword(s):  
Resting State ◽  
Mitochondrial Membrane ◽  
High Rate ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Enzymatic Formation ◽  
Male Sex ◽  
Low Levels ◽  
Cellular Components

AbstractTo proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2as well as of one-electron O2reductants such asThese two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of, and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2and the O2reductants when phosphorylating respiration fails to do this job due to lack of ADP.In particular, it is proposed that some increase in the H+leak of mitochondrial membrane in State 4 lowers, stimulates O2consumption and decreases the level ofwhich otherwise accumulates and serves as one-electron O2reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.

scholarly journals The role of micro-RNAs in the female reproductive tract

Reproduction ◽  
2012 ◽  
Vol 143 (5) ◽  
pp. 559-576 ◽  
Author(s):  
Warren B Nothnick
Keyword(s):  
Posttranslational Modifications ◽  
Reproductive Tract ◽  
Current Knowledge ◽  
Female Reproductive Tract ◽  
Micro Rna ◽  
Proper Function ◽  
Posttranscriptional Gene Regulation ◽  
Micro Rnas ◽  
And Function

Proper development and function of the female reproductive tract are essential for successful reproduction. Regulation of the differentiated functions of the organs that make up the female reproductive tract is well established to occur at multiple levels including transcription, translation, and posttranslational modifications. Micro-RNA (miRNA)-mediated posttranscriptional gene regulation has emerged as a fundamental mechanism controlling normal tissue development and function. Emerging evidence indicates that miRNAs are expressed within the organs of the female reproductive tract where they function to regulate cellular pathways necessary for proper function of these organs. In this review, the functional significance of miRNAs in the development and function of the organs of the female reproductive tract is discussed. Initial discussion focuses on the role of miRNAs in the development of the organs of the female reproductive tract highlighting recent studies that clearly demonstrate that mice with disrupted Dicer1 expression are sterile, fail to develop uterine glands, and have muted estrogen responsiveness. Next, emphasis moves to discussion on our current knowledge on the characterization of miRNA expression in each of the organs of the female reproductive tract. When possible, information is presented and discussed with respect to regulation, function, and/or functional targets of these miRNA within each specific organ of the female reproductive tract.

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