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1.
EMBO J ; 37(21)2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30237312

RESUMO

PGAM5, a mitochondrial protein phosphatase that is genetically and biochemically linked to PINK1, facilitates mitochondrial division by dephosphorylating the mitochondrial fission factor Drp1. At the onset of mitophagy, PGAM5 is cleaved by PARL, a rhomboid protease that degrades PINK1 in healthy cells, and the cleaved form facilitates the engulfment of damaged mitochondria by autophagosomes by dephosphorylating the mitophagy receptor FUNDC1. Here, we show that the function and localization of PGAM5 are regulated by syntaxin 17 (Stx17), a mitochondria-associated membrane/mitochondria protein implicated in mitochondrial dynamics in fed cells and autophagy in starved cells. In healthy cells, loss of Stx17 causes PGAM5 aggregation within mitochondria and thereby failure of the dephosphorylation of Drp1, leading to mitochondrial elongation. In Parkin-mediated mitophagy, Stx17 is prerequisite for PGAM5 to interact with FUNDC1. Our results reveal that the Stx17-PGAM5 axis plays pivotal roles in mitochondrial division and PINK1/Parkin-mediated mitophagy.


Assuntos
Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Mitofagia , Fosfoproteínas Fosfatases/metabolismo , Proteínas Qa-SNARE/metabolismo , Transdução de Sinais , Autofagossomos/metabolismo , Dinaminas , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metaloproteases/genética , Metaloproteases/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/genética , Fosfoproteínas Fosfatases/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteólise , Proteínas Qa-SNARE/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
2.
Breed Sci ; 71(2): 277-282, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34377076

RESUMO

Various types of malt quality profiles have been investigated to benefit the North American brewing industry. Herein, we report the development and brewing quality of the hulled, two-row malting barley (Hordeum vulgare L.) variety 'CDC Goldstar' lacking lipoxygenase-1 (LOX-1-less). This new variety offers a novel malt type for the improvement of beer flavor stability. The agronomic performance of 'CDC Goldstar' was tested in the Western Cooperative Two Row Barley Registration Trials during 2013-2014. In addition to high lodging tolerance, the new variety showed 6% higher yield than the current leading variety 'CDC Copeland'. The malt quality of 'CDC Goldstar' showed higher diastatic power and lower wort ß-glucan content than 'CDC Copeland' and controllable proteolytic modification (soluble nitrogen and Kolbach Index). Pilot- (100 L) and commercial-scale (5,000 L) brewing trials were conducted using 'CDC PlatinumStar', another LOX-1-less variety with a low enzymatic profile, as the control variety. Absence of the LOX-1 trait from 'CDC Goldstar' maintained trans-2-nonenal levels in aged beers as low as those in other LOX-1-less varieties without affecting major beer parameters, such as ester and aldehyde content or foam stability. The newly developed 'CDC Goldstar' malting barley provides added value for the beer industry and consumers.

3.
Dev Cell ; 32(3): 304-17, 2015 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-25619926

RESUMO

Recent evidence suggests that endoplasmic reticulum (ER) tubules mark the sites where the GTPase Drp1 promotes mitochondrial fission via a largely unknown mechanism. Here, we show that the SNARE protein syntaxin 17 (Syn17) is present on raft-like structures of ER-mitochondria contact sites and promotes mitochondrial fission by determining Drp1 localization and activity. The hairpin-like C-terminal hydrophobic domain, including Lys-254, but not the SNARE domain, is important for this regulation. Syn17 also regulates ER Ca(2+) homeostasis and interferes with Rab32-mediated regulation of mitochondrial dynamics. Starvation disrupts the Syn17-Drp1 interaction, thus favoring mitochondrial elongation during autophagy. Because we also demonstrate that Syn17 is an ancient SNARE, our findings suggest that Syn17 is one of the original key regulators for ER-mitochondria contact sites present in the last eukaryotic common ancestor. As such, Syn17 acts as a switch that responds to nutrient conditions and integrates functions for the ER and autophagosomes with mitochondrial dynamics.


Assuntos
Retículo Endoplasmático/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Proteínas Qa-SNARE/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Células HeLa , Humanos , Proteínas Mitocondriais/metabolismo , Fagossomos/metabolismo
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