Fatal attraction-The role of hypoxia when alpha-synuclein gets intimate with mitochondria

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Publications associées (31)

NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle

Johan Auwerx, Hongbo Zhang, Hao Li, Vincenzo Sorrentino, Mario Romani, Changmyung Oh, Tanes Imamura de Lima

Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like d ...

2021

Reverse engineering Lewy bodies: how far have we come and how far can we go?

Hilal Lashuel, Mohamed Bilal Fares, Somanath Jagannath

Lewy bodies (LBs) are α-synuclein (α-syn)-rich intracellular inclusions that are an important pathological hallmark of Parkinson disease and several other neurodegenerative diseases. Increasing evidence suggests that the aggregation of α-syn has a central ...

2021

Disruption of mitochondrial redox homeostasis by enzymatic activation of a trialkylphosphine probe

Jade Noémie Nam Nguyen, Pablo Rivera Fuentes

Redox homeostasis is essential for cell function and its disruption is associated with multiple pathologies. Redox balance is largely regulated by the relative concentrations of reduced and oxidized glutathione. In eukaryotic cells, this ratio is different ...

ROYAL SOC CHEMISTRY2021

Differential roles of GDF15 and FGF21 in systemic metabolic adaptation to the mitochondrial integrated stress response

Johan Auwerx, Jun Yong Kim

Perturbation of mitochondrial proteostasis provokes cell autonomous and cell non-autonomous responses that contribute to homeostatic adaptation. Here, we demonstrate distinct metabolic effects of hepatic metabokines as cell non-autonomous factors in mice w ...

CELL PRESS2021

Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

Maria del Carmen Sandi Perez, Hilal Lashuel, Jean-Christophe Copin, Johannes Burtscher

Increasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studi ...

2020

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

Maria del Carmen Sandi Perez, Rolf Gruetter, Bart Deplancke, Antoine Timothée Cherix, Jocelin Grosse, Julie Marie Russeil, Daniel Alpern, Meltem Weger, Sriparna Ghosal

Mitochondrial dysfunction was highlighted as a crucial vulnerability factor for the development of depression. However, systemic studies assessing stress-induced changes in mitochondria-associated genes in brain regions relevant to depression symptomatolog ...

2020

SLC25A51 is a mammalian mitochondrial NAD(+) transporter

Kai Johnsson, Liang Wang

Mitochondria require nicotinamide adenine dinucleotide (NAD(+)) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD(+) transporters have been identified in yeast and plants(1,2), but thei ...

NATURE RESEARCH2020

The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

Graham Knott, Hilal Lashuel, Mary-Claude Croisier-Coeytaux, Fabien Kuttler, Marion Leleu, Anne-Laure Mahul Mellier, Niran Maharjan, Johannes Burtscher, Laura Emmeline H Weerens

Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, t ...

National Academy of Sciences2020

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells

Loïc Dayon, Isabelle Chareyron, Andreas Wiederkehr, Sofia Moco

Aims/hypothesis In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells durin ...

2020

Astrocytic release of ATP through type 2 inositol 1,4,5‐trisphosphate receptor calcium signaling and social dominance behavior in mice

Maria del Carmen Sandi Perez, Jocelin Grosse, Fiona Hollis, Marie-Isabelle Guillot de Suduiraut, Eva Ramos Fernandez

Brain mitochondrial function is critical for numerous neuronal processes. We recently identified a link between brain energy and social dominance, where higher levels of mitochondrial function resulted in increased social competitive ability. The underlyin ...

2020

Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice

Johan Auwerx, Dongryeol Ryu, Jun Yong Kim, Ludger Jan Elzuë Goeminne

Mitochondrial dysfunction is associated with aging-mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an important mitokine generated in r ...

2020

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