Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Difference between revisions of "De Castro IP 2013 Cell Death Dis"

From Bioblast
Β 
(4 intermediate revisions by 3 users not shown)
Line 1: Line 1:
{{Publication
{{Publication
|title=de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM (2013) ''Drosophila'' ref(2)P is required for the parkin-mediated suppression of mitochondrial dysfunction in pink1 mutants. Cell Death Dis 24:e873
|title=de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM (2013) ''Drosophila'' ref(2)P is required for the ''parkin''-mediated suppression of mitochondrial dysfunction in ''pink1'' mutants. Cell Death Dis 24:e873.
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24157867 PMID: 24157867]
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24157867 PMID: 24157867 Open Access]
|authors=de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM
|authors=de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM
|year=2013
|year=2013
|journal=Cell Death Dis
|journal=Cell Death Dis
|abstract=Autophagy is a critical regulator of organellar homeostasis, particularly of mitochondria. Upon the loss of membrane potential, dysfunctional mitochondria are selectively removed by autophagy through recruitment of the E3 ligase Parkin by the PTEN-induced kinase 1 (PINK1) and subsequent ubiquitination of mitochondrial membrane proteins. Mammalian sequestrome-1 (p62/SQSTM1) is an autophagy adaptor, which has been proposed to shuttle ubiquitinated cargo for autophagic degradation downstream of Parkin. Here, we show that loss of ref(2)P, the ''Drosophila'' orthologue of mammalian P62, results in abnormalities, including mitochondrial defects and an accumulation of mitochondrial DNA with heteroplasmic mutations, correlated with locomotor defects. Furthermore, we show that expression of Ref(2)P is able to ameliorate the defects caused by loss of Pink1 and that this depends on the presence of functional Parkin. Finally, we show that both the PB1 and UBA domains of Ref(2)P are crucial for mitochondrial clustering. We conclude that Ref(2)P is a crucial downstream effector of a pathway involving Pink1 and Parkin and is responsible for the maintenance of a viable pool of cellular mitochondria by promoting their aggregation and autophagic clearance.
|abstract=Autophagy is a critical regulator of organellar homeostasis, particularly of mitochondria. Upon the loss of membrane potential, dysfunctional mitochondria are selectively removed by autophagy through recruitment of the E3 ligase Parkin by the PTEN-induced kinase 1 (PINK1) and subsequent ubiquitination of mitochondrial membrane proteins. Mammalian sequestrome-1 (p62/SQSTM1) is an autophagy adaptor, which has been proposed to shuttle ubiquitinated cargo for autophagic degradation downstream of Parkin. Here, we show that loss of ''ref(2)P'', the ''Drosophila'' orthologue of mammalian ''P62'', results in abnormalities, including mitochondrial defects and an accumulation of mitochondrial DNA with heteroplasmic mutations, correlated with locomotor defects. Furthermore, we show that expression of Ref(2)P is able to ameliorate the defects caused by loss of Pink1 and that this depends on the presence of functional Parkin. Finally, we show that both the PB1 and UBA domains of Ref(2)P are crucial for mitochondrial clustering. We conclude that Ref(2)P is a crucial downstream effector of a pathway involving Pink1 and Parkin and is responsible for the maintenance of a viable pool of cellular mitochondria by promoting their aggregation and autophagic clearance.
|keywords=''Drosophila'', Mitochondria, Parkinson's disease, Stress, Unfolded proteins
|mipnetlab=UK Leicester Martins LM
}}
}}
{{Labeling
{{Labeling
|area=Respiration, Genetic knockout;overexpression, Comparative MiP;environmental MiP
|organism=Drosophila
|preparations=Homogenate
|couplingstates=LEAK, OXPHOS, ET
|pathways=N, S
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=Labels
}}
}}

Latest revision as of 16:30, 9 November 2017

Publications in the MiPMap
de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM (2013) Drosophila ref(2)P is required for the parkin-mediated suppression of mitochondrial dysfunction in pink1 mutants. Cell Death Dis 24:e873.

Β» PMID: 24157867 Open Access

de Castro IP, Costa AC, Celardo I, Tufi R, Dinsdale D, Loh SH, Martins LM (2013) Cell Death Dis

Abstract: Autophagy is a critical regulator of organellar homeostasis, particularly of mitochondria. Upon the loss of membrane potential, dysfunctional mitochondria are selectively removed by autophagy through recruitment of the E3 ligase Parkin by the PTEN-induced kinase 1 (PINK1) and subsequent ubiquitination of mitochondrial membrane proteins. Mammalian sequestrome-1 (p62/SQSTM1) is an autophagy adaptor, which has been proposed to shuttle ubiquitinated cargo for autophagic degradation downstream of Parkin. Here, we show that loss of ref(2)P, the Drosophila orthologue of mammalian P62, results in abnormalities, including mitochondrial defects and an accumulation of mitochondrial DNA with heteroplasmic mutations, correlated with locomotor defects. Furthermore, we show that expression of Ref(2)P is able to ameliorate the defects caused by loss of Pink1 and that this depends on the presence of functional Parkin. Finally, we show that both the PB1 and UBA domains of Ref(2)P are crucial for mitochondrial clustering. We conclude that Ref(2)P is a crucial downstream effector of a pathway involving Pink1 and Parkin and is responsible for the maintenance of a viable pool of cellular mitochondria by promoting their aggregation and autophagic clearance. β€’ Keywords: Drosophila, Mitochondria, Parkinson's disease, Stress, Unfolded proteins

β€’ O2k-Network Lab: UK Leicester Martins LM


Labels: MiParea: Respiration, Genetic knockout;overexpression, Comparative MiP;environmental MiP 


Organism: Drosophila 

Preparation: Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S  HRR: Oxygraph-2k