Mitochondrial division, fusion and degradation Murata, Daisuke; Arai, Kenta; Iijima, Miho ...
Journal of Biochemistry/The journal of biochemistry,
03/2020, Volume:
167, Issue:
3
Journal Article
Peer reviewed
Open access
The mitochondrion is an essential organelle for a wide range of cellular processes, including energy production, metabolism, signal transduction and cell death. To execute these functions, ...mitochondria regulate their size, number, morphology and distribution in cells via mitochondrial division and fusion. In addition, mitochondrial division and fusion control the autophagic degradation of dysfunctional mitochondria to maintain a healthy population. Defects in these dynamic membrane processes are linked to many human diseases that include metabolic syndrome, myopathy and neurodegenerative disorders. In the last several years, our fundamental understanding of mitochondrial fusion, division and degradation has been significantly advanced by high resolution structural analyses, protein-lipid biochemistry, super resolution microscopy and in vivo analyses using animal models. Here, we summarize and discuss this exciting recent progress in the mechanism and function of mitochondrial division and fusion.
In the last few decades, development of novel experimental techniques, such as new types of disulfide (SS)-forming reagents and genetic and chemical technologies for synthesizing designed artificial ...proteins, is opening a new realm of the oxidative folding study where peptides and proteins can be folded under physiologically more relevant conditions. In this review, after a brief overview of the historical and physicochemical background of oxidative protein folding study, recently revealed folding pathways of several representative peptides and proteins are summarized, including those having two, three, or four SS bonds in the native state, as well as those with odd Cys residues or consisting of two peptide chains. Comparison of the updated pathways with those reported in the early years has revealed the flexible nature of the protein folding pathways. The significantly different pathways characterized for hen-egg white lysozyme and bovine milk α-lactalbumin, which belong to the same protein superfamily, suggest that the information of protein folding pathways, not only the native folded structure, is encoded in the amino acid sequence. The application of the flexible pathways of peptides and proteins to the engineering of folded three-dimensional structures is an interesting and important issue in the new realm of the current oxidative protein folding study.
Plant response to drought and hyperosmosis is mediated by the phytohormone abscisic acid (ABA), a sesquiterpene compound widely distributed in various embryophyte groups. Exogenous ABA as well as ...hyperosmosis activates the sucrose nonfermenting 1 (SNF1)-related protein kinase2 (SnRK2), which plays a central role in cellular responses against drought and dehydration, although the details of the activation mechanism are not understood. Analysis of a mutant of the mossPhyscomitrella patenswith reduced ABA sensitivity and reduced hyperosmosis tolerance revealed that a protein kinase designated “ARK” (for “ABA and abiotic stress-responsive Raf-like kinase”) plays an essential role in the activation of SnRK2. ARK encoded by a single gene inP. patensbelongs to the family of group B3 Raf-like MAP kinase kinase kinases (B3-MAPKKKs) mediating ethylene, disease resistance, and salt and sugar responses in angiosperms. Our findings indicate that ARK, as a novel regulatory component integrating ABA and hyperosmosis signals, represents the ancestral B3-MAPKKKs, which multiplied, diversified, and came to have specific functions in angiosperms.
A pressure standard based on the static expansion of gases has been made available at the National Metrology Institute of Japan (NMIJ) for gauge calibrations in the range of 0.1 mPa–2 kPa over the ...past 30 years. The static expansion system (SES) generates calibration pressures by multiple-step gas expansions using two expansion ratios (R900≃907.3 and R50≃53.4). These expansion ratios were determined using the two reference gauges method instead of the one reference gauge method, which has been in use thus far. Relative uncertainties of 0.073% (k = 1) for R900 and 0.036% (k = 1) for R50 were obtained, and the calibration uncertainties were slightly improved compared to the current calibration and measurement capability (CMC) of the SES at NMIJ as follows:U = 0.28% (k = 2) (1 mPa–10 Pa) for spinning rotor gauges (SRGs).U = 0.23% (k = 2) (0.2 Pa–10 Pa) for capacitance diaphragm gauges (CDGs).U = 0.17% (k = 2) (10 Pa–110 Pa) for CDGs.
In addition, the calibration results of the check standards of the past 12 years are reported. The data suggest that the SES was stable compared to the calibration uncertainty over the years.
•Calibration uncertainty of the static expansion system at NMIJ was evaluated.•It is available for vacuum gauge calibrations in the range of 0.1 mPa–2 kPa.•Calibration uncertainty is about 0.3% for SRGs and CDGs.•Its expansion ratios were determined using the two reference gauges method.•Calibration results of the check standards of the past 12 years are reported.
Mitochondria are highly dynamic organelles that continuously grow, divide, and fuse. The division of mitochondria is crucial for human health. During mitochondrial division, the mechano-guanosine ...triphosphatase (GTPase) dynamin-related protein (Drp1) severs mitochondria at endoplasmic reticulum (ER)-mitochondria contact sites, where peripheral ER tubules interact with mitochondria. Here, we report that Drp1 directly shapes peripheral ER tubules in human and mouse cells. This ER-shaping activity is independent of GTP hydrolysis and located in a highly conserved peptide of 18 amino acids (termed D-octadecapeptide), which is predicted to form an amphipathic α helix. Synthetic D-octadecapeptide tubulates liposomes in vitro and the ER in cells. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.
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•Drp1 is associated with the ER•Drp1 shapes the ER into tubules independently of oligomerization and GTP hydrolysis•Octadecapeptide554–571 in the variable domain is sufficient for membrane tubulation•ER tubules formed by Drp1 promote mitochondrial division
Adachi et al. report that Drp1 shapes the ER into tubules independently of GTP hydrolysis. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.
Coupling of thiol and urea-type -NHC(double bond, length as m-dashX)NH2 (X = O or NH) groups is effective in promoting oxidative protein folding. In particular, a thiol compound coupled with a ...guanidyl (X = NH) group significantly accelerates the rates of folding processes and enhances the yields of native proteins.
Glycolipid metabolism occurs in the Golgi apparatus, but the detailed mechanisms have not yet been elucidated. We used fluorescently labeled glycolipids to analyze glycolipid composition and ...localization changes and shed light on glycolipid metabolism. In a previous study, the fatty chain of lactosyl ceramide was fluorescently labeled with BODIPY (LacCer-BODIPY) before being introduced into cultured cells to analyze the cell membrane glycolipid recycling process. However, imaging analysis of glycolipid recycling is difficult because of limited spatial resolution. Therefore, we examined the microscopic conditions that allow the temporal analysis of LacCer-BODIPY trafficking and localization. We observed that the glycolipid fluorescent probe migrated from the cell membrane to intracellular organelles before returning to the cell membrane. We used confocal microscopy to observe co-localization of the glycolipid probe with endosomes and Golgi markers, demonstrating that it recycles mainly through the trans-Golgi network (TGN). Here, a glycolipid recycling pathway was observed that did not require the lipids to pass through the lysosome.
•Visualization of recycling pathways without degradation in lysosomes.•Lysosomal localization of excessive amounts of glycolipid probes.•Time-lapse imaging of glycolipid recycling.•Multicolor imaging of Golgi stacks and trans-Golgi networks.
Adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) (AK) is the enzyme that catalyzes the reversible conversion of MgATP + AMP to MgADP + ADP, a principal step in adenine nucleotide metabolism ...and cellular energy homeostasis. To enrich the information about fish AKs, we isolated this enzyme from the lateral muscle of bastard halibut
Paralichthys olivaceus
and biochemically characterized it. The halibut enzyme (PoAK) extracted from the lateral muscle was purified by column chromatographies on TOYOPEARL SP-650 M and Superdex 75 10/300. The purified PoAK showed a single protein band of ~ 22 kDa on SDS–polyacrylamide gel electrophoresis, and optimal temperature and pH at around 40 °C and 7, respectively. PoAK was appreciably heat stable, e.g., the temperature that caused 50% inactivation during 30-min incubation was 54 °C. The molar ratio for ATP:ADP:AMP in the equilibrium state of the reaction was ~ 1:1:1. Peptide mass fingerprinting indicated that PoAK is the product of adenylate kinase isoform 1 gene (GenBank, XP_019937160.1) encoded in the halibut genome. The deduced amino-acid sequence of the halibut AK comprised 194 residues and showed 92, 91 and 81% amino-acid identities to those of a putative rainbow trout AK, a carp AK and a chicken AK, respectively.
We previously reported that water-soluble cyclic selenides can mimic the antioxidative function of glutathione peroxidase (GPx) in water through a simple catalytic cycle, in which the selenide (>Se) ...is oxidized by H₂O₂ to the selenoxide (>Se=O) and the selenoxide is reduced by a thiol back to the selenide. In methanol, however, the GPx-like activity could not be explained by this simple scenario. To look into the reasons for the unusual behaviors in methanol, monoamino-substituted cyclic selenides with a variable ring size were synthesized, and the intermediates of the catalytic cycle were characterized by means of
Se-NMR and LC-MS spectroscopies. In water, it was confirmed that the selenide and the selenoxide mainly contribute to the antioxidative function, though a slight contribution from the dihydroxy selenane (>Se(OH)₂) was also suggested. In methanol, on the other hand, other active species, such as hydroxyselenonium (>Se⁺-OH) and hydroxy perhydroxy selenane (>Se(OH)(OOH)), could be generated to build another catalytic cycle. This over-oxidation would be more feasible for amino-substituted cyclic selenides, probably because the ammonium (NH₃⁺) group would transfer a proton to the selenoxide moiety to produce a hydroxyselenonium species in the absence of an additional proton source. Thus, a shift of the major catalytic cycle in methanol would make the GPx-like antioxidative function of selenides perplexing.
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