A5041781193- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Metabolism and Genetic Disorders
- Viral-associated cancers and disorders
- Endoplasmic Reticulum Stress and Disease
- Immune Cell Function and Interaction
- Lysosomal Storage Disorders Research
- interferon and immune responses
- ATP Synthase and ATPases Research
- RNA regulation and disease
- Neurological disorders and treatments
- Retinoids in leukemia and cellular processes
- Alzheimer's disease research and treatments
- Lipid metabolism and biosynthesis
University of Padua
2018-2025
Ospedale generale di zona San Camillo Treviso
2018-2019
IRCCS San Camillo Hospital
2018
Parkin, an E3 ubiquitin ligase and a Parkinson's disease (PD) related gene, translocates to impaired mitochondria drives their elimination via autophagy, process known as mitophagy. Mitochondrial pro-fusion protein Mitofusins (Mfn1 Mfn2) were found be target for Parkin mediated ubiquitination. Mfns are transmembrane GTPase embedded in the outer membrane of mitochondria, which required on adjacent mediate fusion. In mammals, Mfn2 also forms complexes that capable tethering endoplasmic...
Research Article24 September 2018Open Access Source DataTransparent process USP14 inhibition corrects an in vivo model of impaired mitophagy Joy Chakraborty Department Biology, University Padova, Italy Search for more papers by this author Sophia von Stockum Fondazione Ospedale San Camillo IRCCS, Venezia, Italia Elena Marchesan Federico Caicci Vanni Ferrari Aleksandar Rakovic Institute Neurogenetics, Lübeck, Germany Christine Klein Angelo Antonini Neuroscience, Luigi Bubacco Ziviani...
Abstract Selective removal of dysfunctional mitochondria via autophagy is crucial for the maintenance cellular homeostasis. This event initiated by translocation E3 ubiquitin ligase Parkin to damaged mitochondria, and it requires Serine/Threonine-protein kinase PINK1. In a coordinated set events, PINK1 operates upstream in linear pathway that leads phosphorylation Parkin, Ubiquitin, mitochondrial substrates, promote ubiquitination outer membrane proteins. Ubiquitin-decorated are selectively...
Abstract Mitochondria are essential organelles and their functional state dictates cellular proteostasis. However, little is known about the molecular gatekeepers involved, especially in absence of external stress. Here we identify a role MFN2 quality control independent its function organellar shape remodeling. ablation alters proteome, marked for example by decreased levels import machinery accumulation kinase PINK1. Moreover, interacts with proteasome cytosolic chaperones, thereby...
Abstract Friedreich ataxia (FRDA) is a rare, inherited neurodegenerative disease caused by an expanded GAA repeat in the first intron of FXN gene, leading to transcriptional silencing and reduced expression frataxin. Frataxin participates mitochondrial assembly FeS clusters, redox cofactors respiratory complexes I, II III. To date it still unclear how frataxin deficiency culminates decrease bioenergetics efficiency FRDA patients’ cells. We previously demonstrated that healthy cells closely...
Dysregulations of mitochondria with alterations in trafficking and morphology these organelles have been related to Parkinson’s disease (PD), a neurodegenerative disorder characterized by brain accumulation Lewy bodies (LB), intraneuronal inclusions mainly composed α -synuclein ( -syn) fibrils. Experimental evidence supports that -syn pathological aggregation can negatively impinge on mitochondrial functions suggesting this protein may be crucially involved the control homeostasis. The aim...
Aberrant mitochondrial dynamics disrupts function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional fusion Mitofusin (MFN) identified USP8 prominently influencing MFN levels. Genetic pharmacological inhibition normalized the elevated observed in PINK1 Parkin-deficient models. This correlated with improved function, locomotor performance life span, prevented dopaminergic neurons loss...
UCH-L1 is a deubiquitinating enzyme (DUB), highly abundant in neurons, with sub-cellular localization dependent on its farnesylation state. Despite UCH-L1′s association familial Parkinson's Disease (PD), the effects mitochondrial bioenergetics and quality control remain unexplored. Here we investigated role of UCHL-1 dynamics bioenergetics. We demonstrate that knock-down (KD) different cell lines reduces levels fusion protein Mitofusin-2, but not Mitofusin-1, resulting enlargement disruption...
Abstract Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, sleep disturbance, no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due haploinsufficiency of the retinoic acid-induced-1 ( RAI1 ) gene caused either chromosomal deletion (SMS-del) missense/nonsense mutation. The molecular mechanisms underlying are unknown. Here, we generated primary cells derived from four patients (two...
Exposure of inner mitochondrial membrane resident protein PHB2 (prohibitin 2) during autophagic removal depolarized mitochondria (mitophagy) depends on the ubiquitin-proteasome system. This uncovering facilitates interaction with phagophore membrane-associated MAP1LC3/LC3. It is unclear whether exposed randomly at rupture sites. Prior knowledge and initial screening indicated that VDAC1 (voltage dependent anion channel 1) might play a role in this phenomenon. Through vitro biochemical assays...
Abstract Selective removal of dysfunctional mitochondria via autophagy is crucial for the maintenance cellular homeostasis. This event initiated by translocation E3 ubiquitin ligase Parkin to damaged mitochondria, and it requires Serine/Threonine-protein kinase PINK1. In a coordinated set events, PINK1 operates upstream in linear pathway that leads phosphorylation Parkin, Ubiquitin, mitochondrial substrates, promote ubiquitination outer membrane proteins. Ubiquitin decorated are selectively...
Abstract Autophagic elimination of depolarized mitochondria (mitophagy) depends on Ubiquitin proteasome complex to expose the inner mitochondrial membrane-resident protein-Prohibitin 2 (PHB2). This uncovering facilitates its interaction with autophagosomal membrane-associated protein LC3. It remains unclear whether PHB2 is uncovered randomly through rupture sites. Prior knowledge and initial screening indicated that Voltage-dependent anion-selective channel 1 (VDAC1) might play a role in...
Abstract Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, sleep disorder. There no therapy to alleviate symptoms or delay disease onset. SMS due the haploinsufficiency of retinoic-acid-induced-1 gene ( RAI1 ) caused either chromosomal deletions (SMS-del) missense/nonsense mutations. The molecular mechanisms underlying are not known. Here we generated primary cells derived from four patients, two carrying SMS-del, with...
Abstract Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, sleep disturbance. There no therapy to alleviate its symptoms or delay disease onset. SMS occurs due haploinsufficiency of the retinoic acid-induced-1 ( RAI1 ) gene caused either chromosomal deletion (SMS-del) missense/nonsense mutation. The molecular mechanisms underlying are not known. Here, we generated primary cells derived from four patients, two carrying...