A new mutation in the Parkinson's‐related FBXO7 gene impairs mitochondrial and proteasomal function DOI Creative Commons
Elisa Navarro, Noemí Esteras

FEBS Journal, Год журнала: 2024, Номер 291(12), С. 2562 - 2564

Опубликована: Май 6, 2024

Around 10% of Parkinson's disease (PD) cases are associated with mutations in various genes, including FBXO7 , which encodes the substrate‐recognition component for Skp1‐Cullin‐F‐box (SCF) class ubiquitin E3 ligases that target proteins proteasomal degradation. In their recent study, Al Rawi et al . characterized a new mutation L250P, pediatric patient. Their findings reveal L250P abolishes Fbxo7 interaction proteasome regulator, inhibitor 31kD (PI31), affecting activity and ubiquitination some ligase's targets. Furthermore, authors show this previously undescribed impairs mitochondrial function mitophagy, emphasizing importance dysfunction PD pathogenesis.

Язык: Английский

PARK15/FBXO7 is dispensable for PINK1/Parkin mitophagy in iNeurons and HeLa cell systems DOI Creative Commons
Felix Kraus, Ellen A. Goodall, Ian R. Smith

и другие.

EMBO Reports, Год журнала: 2023, Номер 24(8)

Опубликована: Июнь 19, 2023

The protein kinase PINK1 and ubiquitin ligase Parkin promote removal of damaged mitochondria via a feed-forward mechanism involving (Ub) phosphorylation (pUb), activation, ubiquitylation mitochondrial outer membrane proteins to support the recruitment mitophagy receptors. substrate receptor FBXO7/PARK15 is mutated in an early-onset parkinsonian-pyramidal syndrome. Previous studies have proposed role for FBXO7 promoting Parkin-dependent mitophagy. Here, we systematically examine involvement depolarization

Язык: Английский

Процитировано

14
PI31 is a positive regulator of 20S immunoproteasome assembly DOI Creative Commons

Jason Wang,

Abbey Kjellgren,

George Demartino

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

PI31 ( P roteasome Inhibitor of 31 ,000 Da) is a 20S proteasome-binding protein originally identified as an inhibitor in vitro proteasome activity. Although recent studies have provided detailed structural basis for this activity, the physiologic significance PI31-mediated inhibition remains uncertain and alternative cellular roles been described. Here we report role positive regulator assembly immuno-proteasome (20Si), compositionally functionally distinct isoform that poorly inhibited by PI31. Genetic ablation mammalian cells had no effect on content or activity constitutively expressed proteasomes but reduced interferon-γ-induced immuno-proteasomes. This selective consequence defective 20Si assembly, indicated accumulation intermediates. Our results highlight distinction pathways constitutive immuno-proteasomes indicate plays chaperone-like immunoproteasomes.

Язык: Английский

Процитировано

0
PSMF1variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways DOI Creative Commons

Francesca Magrinelli,

Christelle Tesson,

Plamena R. Angelova

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 20, 2024

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes identification potential biomarkers therapeutic targets. Here, we identify

Язык: Английский

Процитировано

2
A new mutation in the Parkinson's‐related FBXO7 gene impairs mitochondrial and proteasomal function DOI Creative Commons
Elisa Navarro, Noemí Esteras

FEBS Journal, Год журнала: 2024, Номер 291(12), С. 2562 - 2564

Опубликована: Май 6, 2024

Around 10% of Parkinson's disease (PD) cases are associated with mutations in various genes, including FBXO7 , which encodes the substrate‐recognition component for Skp1‐Cullin‐F‐box (SCF) class ubiquitin E3 ligases that target proteins proteasomal degradation. In their recent study, Al Rawi et al . characterized a new mutation L250P, pediatric patient. Their findings reveal L250P abolishes Fbxo7 interaction proteasome regulator, inhibitor 31kD (PI31), affecting activity and ubiquitination some ligase's targets. Furthermore, authors show this previously undescribed impairs mitochondrial function mitophagy, emphasizing importance dysfunction PD pathogenesis.

Язык: Английский

Процитировано

1