TY - JOUR
A1 - Leong, Jia Xuan
A1 - Raffeiner, Margot
A1 - Spinti, Daniela
A1 - Langin, Gautier
A1 - Franz-Wachtel, Mirita
A1 - Guzman, Andrew R.
A1 - Kim, Jung-Gun
A1 - Pandey, Pooja
A1 - Minina, Alyona E.
A1 - Macek, Boris
A1 - Hafren, Anders
A1 - Bozkurt, Tolga O.
A1 - Mudgett, Mary Beth
A1 - Börnke, Frederik
A1 - Hofius, Daniel
A1 - Uestuen, Suayib
T1 - A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component
JF - The EMBO journal
N2 - Beyond its role in cellular homeostasis, autophagy plays anti- and promicrobial roles in host-microbe interactions, both in animals and plants.
One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy.
Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination.
Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown.
Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection.
Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery.
Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense-related autophagy in plant-bacteria interactions.
KW - autophagy
KW - effectors
KW - immunity
KW - ubiquitination
KW - xenophagy
Y1 - 2022
U6 - https://doi.org/10.15252/embj.2021110352
SN - 1460-2075
VL - 41
IS - 13
PB - Wiley
CY - Hoboken
ER -
TY - JOUR
A1 - Wiedmer, Petra
A1 - Jung, Tobias
A1 - Castro, Jose Pedro
A1 - Pomatto, Laura C. D.
A1 - Sun, Patrick Y.
A1 - Davies, Kelvin J. A.
A1 - Grune, Tilman
T1 - Sarcopenia
BT - molecular mechanisms and open questions
JF - Ageing research reviews : ARR
N2 - Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength occurring during normal aging. Sarcopenia patients are mainly suffering from the loss in muscle strength and are faced with mobility disorders reducing their quality of life and are, therefore, at higher risk for morbidity (falls, bone fracture, metabolic diseases) and mortality.
Several molecular mechanisms have been described as causes for sarcopenia that refer to very different levels of muscle physiology. These mechanisms cover e. g. function of hormones (e. g. IGF-1 and Insulin), muscle fiber composition and neuromuscular drive, myo-satellite cell potential to differentiate and proliferate, inflammatory pathways as well as intracellular mechanisms in the processes of proteostasis and mitochondrial function.
In this review, we describe sarcopenia as a muscle-wasting syndrome distinct from other atrophic diseases and summarize the current view on molecular causes of sarcopenia development as well as open questions provoking further research efforts for establishing efficient lifestyle and therapeutic interventions.
KW - molecular pathways
KW - proteostasis
KW - proteasome
KW - autophagy
KW - mitochondria,
KW - muscle fibre composition
Y1 - 2020
U6 - https://doi.org/10.1016/j.arr.2020.101200
SN - 1568-1637
SN - 1872-9649
VL - 65
PB - Elsevier
CY - Clare
ER -
TY - THES
A1 - Laeger, Thomas
T1 - Protein-dependent regulation of feeding, metabolism, and development of type 2 diabetes
T1 - Proteinabhängige Regulation der Nahrungsaufnahme und des Metabolismus sowie Entstehung des Typ-2-Diabetes
BT - FGF21’s biological role
BT - die Rolle von FGF21
N2 - Food intake is driven by the need for energy but also by the demand for essential nutrients such as protein. Whereas it was well known how diets high in protein mediate satiety, it remained unclear how diets low in protein induce appetite. Therefore, this thesis aims to contribute to the research area of the detection of restricted dietary protein and adaptive responses.
This thesis provides clear evidence that the liver-derived hormone fibroblast growth factor 21 (FGF21) is an endocrine signal of a dietary protein restriction, with the cellular amino acid sensor general control nonderepressible 2 (GCN2) kinase acting as an upstream regulator of FGF21 during protein restriction. In the brain, FGF21 is mediating the protein-restricted metabolic responses, e.g. increased energy expenditure, food intake, insulin sensitivity, and improved glucose homeostasis. Furthermore, endogenous FGF21 induced by dietary protein or methionine restriction is preventing the onset of type 2 diabetes in the New Zealand Obese mouse.
Overall, FGF21 plays an important role in the detection of protein restriction and macronutrient imbalance in rodents and humans, and mediates both the behavioral and metabolic responses to dietary protein restriction. This makes FGF21 a critical physiological signal of dietary protein restriction, highlighting the important but often overlooked impact of dietary protein on metabolism and eating behavior, independent of dietary energy content.
N2 - Die Nahrungsaufnahme wird nicht nur durch den Bedarf an Energie, sondern auch durch den Bedarf an essenziellen Nährstoffen wie z. B. Protein bestimmt. Es war zwar bekannt, wie proteinreiche Nahrung eine Sättigung vermittelt, jedoch war unklar, wie eine proteinarme Ernährung den Appetit anregt. Ziel dieser Arbeit ist es daher, zu untersuchen, wie Nahrung mit einem niedrigen Proteingehalt detektiert wird und die Anpassung des Organismus im Hinblick auf den Metabolismus und das Ernährungsverhalten erfolgt.
Diese Arbeit liefert klare Beweise dafür, dass das aus der Leber stammende Hormon Fibroblast growth factor 21 (FGF21) ein endokrines Signal einer Nahrungsproteinrestriktion ist, wobei der zelluläre Aminosäuresensor general control nonderepressible 2 kinase (GCN2) als Regulator von FGF21 während der Proteinrestriktion fungiert. Im Gehirn vermittelt FGF21 die durch Proteinrestriktion induzierten Stoffwechselreaktionen, z.B. den Anstieg des Energieverbrauches, die Erhöhung der Nahrungsaufnahme und eine Verbesserung der Insulinsensitivität sowie der Glukosehomöostase. Darüber hinaus schützt das durch eine protein- oder methioninarme Diät induzierte FGF21 New Zealand Obese (NZO)-Mäuse, einem Tiermodell für den humanen Typ-2-Diabetes, vor einer Diabetesentstehung.
FGF21 spielt bei Nagetieren und Menschen eine wichtige Rolle hinsichtlich der Detektion einer diätetischen Proteinrestriktion sowie eines Ungleichgewichtes der Makronährstoffe zueinander und vermittelt die adaptiven Verhaltens- und Stoffwechselreaktionen. Dies macht FGF21 zu einem kritischen physiologischen Signal der Nahrungsproteinrestriktion und unterstreicht den wichtigen, aber oft übersehenen Einfluss der Nahrungsproteine auf den Stoffwechsel und das Nahrungsaufnahmeverhalten, unabhängig vom Energiegehalt der Nahrung.
KW - protein restriction
KW - autophagy
KW - thermogenesis
KW - appetite
KW - hyperglycemia
KW - methionine restriction
KW - bone
KW - FGF21
KW - energy expenditure
KW - GCN2
KW - metabolism
KW - food choice
KW - type 2 diabetes
Y1 - 2021
ER -