Fabienne C. Fiesel
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View article: Distinct PINK1‐PRKN mitophagy alterations in different primary tauopathies
Distinct PINK1‐PRKN mitophagy alterations in different primary tauopathies Open
Background Mitophagy constitutes a crucial cellular pathway in mitochondrial quality control, in which the enzymatic pair PINK1 and PRKN selectively decorates damaged mitochondria with phosphorylated‐ubiquitin (pS65‐Ub), facilitating their…
View article: Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase
Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase Open
Loss-of-function mutations in the PINK1 and PRKN genes are the most common cause of early-onset Parkinson disease (PD). The encoded enzymatic pair selectively identifies, labels, and targets damaged mitochondria for degradation via the mac…
View article: The many connections of UFMylation with Alzheimer’s disease: a comprehensive review
The many connections of UFMylation with Alzheimer’s disease: a comprehensive review Open
Alzheimer’s disease (AD) is a complex neurodegenerative disorder that is characterized by the accumulation of pathologic tau and beta-amyloid proteins. UFMylation is an emerging ubiquitin-like post-translational modification that is crucia…
View article: Genome‐wide association analysis identifies <i>APOE</i> as a mitophagy modifier in Lewy body disease
Genome‐wide association analysis identifies <i>APOE</i> as a mitophagy modifier in Lewy body disease Open
INTRODUCTION Phosphorylated ubiquitin (p‐S65‐Ub) is generated during PINK1‐PRKN mitophagy as a specific marker of mitochondrial damage. Despite the widespread deposition of p‐S65‐Ub in aged and diseased human brain, the genetic contributio…
View article: Development and validation of a sensitive sandwich ELISA against human PINK1
Development and validation of a sensitive sandwich ELISA against human PINK1 Open
The ubiquitin kinase and ligase PINK1 and PRKN together label damaged mitochondria for their elimination in lysosomes by selective autophagy (mitophagy). This cytoprotective quality control pathway is genetically linked to familial Parkins…
View article: Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain
Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain Open
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson’s disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 …
View article: Phosphorylated Ubiquitin as a Clinical Biomarker for Mitochondrial Damage in Neurodegenerative Diseases
Phosphorylated Ubiquitin as a Clinical Biomarker for Mitochondrial Damage in Neurodegenerative Diseases Open
Phosphorylated ubiquitin (pS65-Ub) is generated by the kinase-ligase pair PINK1-Parkin to selectively label damaged mitochondria for degradation via the autophagy-lysosome system (mitophagy). Consistent with increasing mitochondrial and ly…
View article: NLRP3 Inflammasome Activation and Altered Mitophagy Are Key Pathways in Inclusion Body Myositis
NLRP3 Inflammasome Activation and Altered Mitophagy Are Key Pathways in Inclusion Body Myositis Open
Background Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. In this study, we aimed to explore the interplay between inflamm…
View article: Alterations of PINK1-PRKN signaling in mice during normal aging
Alterations of PINK1-PRKN signaling in mice during normal aging Open
The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon a…
View article: Identification of tau UFMylation <i>in vitro and in vivo</i>
Identification of tau UFMylation <i>in vitro and in vivo</i> Open
Background UFMylation is an understudied ubiquitin‐like post‐translational modification (PTM). Like ubiquitin, UFM1 is conjugated to substrates via a catalytic cascade involving a UFM1‐specific E1 (UBA5), E2 (UFC1), and an E3 ligase comple…
View article: Synergistic effects of α‐synuclein, tau, and amyloid pathology on mitophagy in dementia with Lewy bodies
Synergistic effects of α‐synuclein, tau, and amyloid pathology on mitophagy in dementia with Lewy bodies Open
Background Directed by the enzyme pair PINK1 and PRKN, mitophagy is a crucial mitochondrial quality control mechanism that selectively decorates damaged mitochondria with phosphorylated ubiquitin (pS65‐Ub), facilitating their lysosomal deg…
View article: Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W
Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W Open
Mutations in the PINK1 and PRKN genes are the most frequent genetic cause of early-onset Parkinson disease. The pathogenic p.R275W substitution in PRKN is the most frequent substitution observed in patients, and thus far has been character…
View article: p-S65-Ub sandwich ELISA v1
p-S65-Ub sandwich ELISA v1 Open
Here we describe an assay to measure the levels of phosphorylation of Ubiquitin at Serine-65 in vivo by enzyme linked immunosorbent assay (ELISA). This assay was previously described by Watzlawik and colleagues [https://doi.org/10.1080/155…
View article: NLRP3 inflammasome activation and altered mitophagy are key pathways in inclusion body myositis
NLRP3 inflammasome activation and altered mitophagy are key pathways in inclusion body myositis Open
Background Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. Inflammation and mitochondrial dysfunction are the most common h…
View article: Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain
Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain Open
Mutations in LRRK2 and PINK1 are associated with familial Parkinson’s disease (PD). LRRK2 phosphorylates Rab GTPases within the Switch II domain whilst PINK1 directly phosphorylates Parkin and ubiquitin and indirectly induces phosphorylati…
View article: Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue
Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue Open
The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy path…
View article: The UFMylation pathway is impaired in Alzheimer’s disease
The UFMylation pathway is impaired in Alzheimer’s disease Open
Background Alzheimer’s disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogene…
View article: Alterations of PINK1-PRKN signaling in mice during normal aging
Alterations of PINK1-PRKN signaling in mice during normal aging Open
The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon a…
View article: In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling
In Silico Investigation of Parkin-Activating Mutations Using Simulations and Network Modeling Open
Complete loss-of-function mutations in the PRKN gene are a major cause of early-onset Parkinson’s disease (PD). PRKN encodes the Parkin protein, an E3 ubiquitin ligase that works in conjunction with the ubiquitin kinase PINK1 in a distinct…
View article: miRNA family miR-29 inhibits PINK1-PRKN dependent mitophagy via ATG9A
miRNA family miR-29 inhibits PINK1-PRKN dependent mitophagy via ATG9A Open
Loss-of-function mutations in the genes encoding PINK1 and PRKN result in early-onset Parkinson disease (EOPD). Together the encoded enzymes direct a neuroprotective pathway that ensures the elimination of damaged mitochondria via autophag…
View article: Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue
Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue Open
The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy path…
View article: Basal activity of PINK1 and PRKN in cell models and rodent brain
Basal activity of PINK1 and PRKN in cell models and rodent brain Open
The ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN functio…
View article: Genome‐wide analysis identifies APOE4 as a strong mitophagy modifier in Lewy body disease
Genome‐wide analysis identifies APOE4 as a strong mitophagy modifier in Lewy body disease Open
Background Loss of function mutations in PINK1 and PRKN are the most common causes of early‐onset Parkinson disease (PD). The encoded ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase PRKN together regulate the autophagic degradation of dys…
View article: Dysregulation of UFMylation pathway in Alzheimer’s disease
Dysregulation of UFMylation pathway in Alzheimer’s disease Open
Background Neuropathologically, Alzheimer’s disease (AD) is characterized by the presence of senile plaques composed of beta‐amyloid (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau. Aβ and p‐tau have been shown to impact e…
View article: Genome-wide association study identifies<i>APOE</i>and<i>ZMIZ1</i>variants as mitophagy modifiers in Lewy body disease
Genome-wide association study identifies<i>APOE</i>and<i>ZMIZ1</i>variants as mitophagy modifiers in Lewy body disease Open
The PINK1-PRKN pathway mediates a critical quality control to maintain mitochondrial health and function. Together the kinase-ligase pair identifies and decorate damaged mitochondria with phosphorylated ubiquitin (p-S65-Ub). This selective…
View article: Interplay of Impaired Cellular Bioenergetics and Autophagy in PMM2-CDG
Interplay of Impaired Cellular Bioenergetics and Autophagy in PMM2-CDG Open
Congenital disorders of glycosylation (CDG) and mitochondrial disorders are multisystem disorders with overlapping symptomatology. Pathogenic variants in the PMM2 gene lead to abnormal N-linked glycosylation. This disruption in glycosylati…
View article: Alpha‐synuclein‐associated changes in PINK1‐PRKN‐mediated mitophagy are disease context dependent
Alpha‐synuclein‐associated changes in PINK1‐PRKN‐mediated mitophagy are disease context dependent Open
Alpha‐synuclein (αsyn) aggregates are pathological features of several neurodegenerative conditions including Parkinson disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA). Accumulating evidence suggests that mitocho…