scholarly journals Mitochondrial K+ Transport: Modulation and Functional Consequences

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2935
Author(s):  
Osvaldo Pereira ◽  
Alicia J. Kowaltowski
Keyword(s):  
Ischemia Reperfusion ◽  
K Channel ◽  
Cellular Processes ◽  
Molecular Identity ◽  
Cellular Events ◽  
Functional Consequences ◽  
Mitochondrial Volume ◽  
Transport Modulation ◽  
K Transport

The existence of a K+ cycle in mitochondria has been predicted since the development of the chemiosmotic theory and has been shown to be crucial for several cellular phenomena, including regulation of mitochondrial volume and redox state. One of the pathways known to participate in K+ cycling is the ATP-sensitive K+ channel, MitoKATP. This channel was vastly studied for promoting protection against ischemia reperfusion when pharmacologically activated, although its molecular identity remained unknown for decades. The recent molecular characterization of MitoKATP has opened new possibilities for modulation of this channel as a mechanism to control cellular processes. Here, we discuss different strategies to control MitoKATP activity and consider how these could be used as tools to regulate metabolism and cellular events.

scholarly journals Pathogenesis of Mucopolysaccharidoses, an Update

2020 ◽  
Vol 21 (7) ◽  
pp. 2515 ◽  
Author(s):  
Simona Fecarotta ◽  
Antonietta Tarallo ◽  
Carla Damiano ◽  
Nadia Minopoli ◽  
Giancarlo Parenti
Keyword(s):  
Clinical Manifestations ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Cellular Events ◽  
New Information ◽  
New Vision ◽  
And Function ◽  
And Oxidative Stress ◽  
Novel Therapeutic

The recent advancements in the knowledge of lysosomal biology and function have translated into an improved understanding of the pathophysiology of mucopolysaccharidoses (MPSs). The concept that MPS manifestations are direct consequences of lysosomal engorgement with undegraded glycosaminoglycans (GAGs) has been challenged by new information on the multiple biological roles of GAGs and by a new vision of the lysosome as a signaling hub involved in many critical cellular functions. MPS pathophysiology is now seen as the result of a complex cascade of secondary events that lead to dysfunction of several cellular processes and pathways, such as abnormal composition of membranes and its impact on vesicle fusion and trafficking; secondary storage of substrates; impairment of autophagy; impaired mitochondrial function and oxidative stress; dysregulation of signaling pathways. The characterization of this cascade of secondary cellular events is critical to better understand the pathophysiology of MPS clinical manifestations. In addition, some of these pathways may represent novel therapeutic targets and allow for the development of new therapies for these disorders.

Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events

2016 ◽  
Vol 23 (19) ◽  
pp. 1965-1980 ◽  
Author(s):  
Branislav Rovcanin ◽  
Branislava Medic ◽  
Gordana Kocic ◽  
Tatjana Cebovic ◽  
Marko Ristic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Molecular Dissection ◽  
Cellular Events

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

scholarly journals Characterization of SARS-CoV-2 N protein reveals multiple functional consequences of the C-terminal domain

iScience ◽  
2021 ◽  
pp. 102681
Author(s):  
Chao Wu ◽  
Abraham J. Qavi ◽  
Asmaa Hachim ◽  
Niloufar Kavian ◽  
Aidan R. Cole ◽  
...  
Keyword(s):  
N Protein ◽  
Terminal Domain ◽  
Functional Consequences

scholarly journals Characterization of adenosine deaminase (ADA) in Hemolymph of Biomphalaria glabrata

2005 ◽  
Vol 65 (2) ◽  
pp. 371-376 ◽  
Author(s):  
M. R. Vale ◽  
R. V. Pereira ◽  
S. M. Almeida ◽  
Y. M. Almeida ◽  
S. F. L. C. Nunes
Keyword(s):  
Adenosine Deaminase ◽  
Incubation Temperature ◽  
Small Variation ◽  
Healthy Human ◽  
Ph Variation ◽  
Cellular Events ◽  
Low Concentrations ◽  
Key Enzyme ◽  
Assay Conditions

Adenosine is an important signaling molecule for many cellular events. Adenosine deaminase (ADA) is a key enzyme for the control of extra- and intra-cellular levels of adenosine. Activity of ADA was detected in hemolymph of B. glabrata and its optimum assay conditions were determined experimentally. The pH variation from 6.2 to 7.8 caused no significant change in ADA activity. Using adenosine as a substrate, the apparent Km at pH 6.8 was 734 µmols.L-1. Highest activity was found at 37ºC. Standard assay conditions were established as being 15 minutes of incubation time, 0.4 µL of pure hemolymph per assay, pH 6.8, and 37ºC. This enzyme showed activities of 834 ± 67 µmol.min-1.L-1 (25ºC) and 2029 ± 74 µmol.min-1.L-1 (37ºC), exceeding those in healthy human serum by 40 and 100 times, respectively. Higher incubation temperature caused a decrease in activity of 20% at 43ºC or 70% at 50ºC for 15 minutes. The ADA lost from 26 to 78% of its activity when hemolymph was pre-incubated at 50ºC for 2 or 15 minutes, respectively. Since the ADA from hemolymph presented high levels, it can be concluded that in healthy and fed animals, adenosine is maintained at low concentrations. In addition, the small variation in activity over the 6.2 to 7.8 range of pH suggests that adenosine is maintained at low levels in hemolymph even under adverse conditions, in which the pH is altered.

scholarly journals Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats

2018 ◽  
Vol 314 (4) ◽  
pp. F584-F601 ◽  
Author(s):  
Siree Asvapromtada ◽  
Hiroko Sonoda ◽  
Minami Kinouchi ◽  
Sayaka Oshikawa ◽  
Saki Takahashi ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Interacting Protein ◽  
Aquaporin 1 ◽  
Water Handling ◽  
Marker Proteins ◽  
Apical Trafficking ◽  
Renal Expression

Acute kidney injury (AKI) is an important risk factor for the development of chronic kidney disease (CKD), and an alteration in renal water handling has been observed during the transition of AKI to CKD. Urinary exosomal release of aquaporin-1 (AQP1) and AQP2, important proteins for renal water handling, has recently been reported to predict their levels of renal expression. Therefore, we examined the patterns of urinary exosomal release of AQP1 and AQP2, and the exosomal marker proteins tumor susceptibility 101 protein (TSG101) and ALG-2 interacting protein X (Alix), in the acute and chronic phases following induction of AKI by renal bilateral ischemia/reperfusion (I/R) in rats. Blood tests and histological examinations indicated that AKI occurred before at 7 days after renal I/R ( day 7) and that renal fibrosis developed progressively thereafter. Immunoblotting demonstrated significant decreases in the urinary exosomal release of AQP1 and AQP2 during severe AKI. Urinary exosomal release of Alix and TSG101 was significantly increased on day 7. These data were also confirmed in rats with unilateral renal I/R causing more serious AKI. Urinary exosomal release of either the Ser-256- or Ser-269-phosphorylated form of AQP2, both of which are involved in apical trafficking of AQP2, was positively correlated with that of total AQP2. These results suggest that urinary exosomal release of AQP1 and AQP2 is reduced in I/R-induced AKI, whereas that of Alix and TSG101 is increased in the initial phase of renal fibrosis. Furthermore, apical trafficking of AQP2 appears to be related to urinary exosomal release of AQP2.

scholarly journals Characterization of a Chloroplast Inner Envelope K+ Channel

1994 ◽  
Vol 105 (3) ◽  
pp. 955-964 ◽  
Author(s):  
F. Mi ◽  
J. S. Peters ◽  
G. A. Berkowitz
Keyword(s):  
K Channel ◽  
Inner Envelope

scholarly journals TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria

2016 ◽  
Vol 473 (2) ◽  
pp. 107-121 ◽  
Author(s):  
Jemma Gatliff ◽  
Michelangelo Campanella
Keyword(s):  
Neurological Diseases ◽  
Anion Channel ◽  
Translocator Protein ◽  
Endocrine Regulation ◽  
Voltage Dependent Anion Channel ◽  
Steroid Synthesis ◽  
Cellular Processes ◽  
Cellular Events ◽  
Voltage Dependent

The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review.

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