DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7

Michela Di Nottia, M Masciullo, D Verrigni, S Petrillo, A. Modoni, V Rizzo, D. Di Giuda, T Rizza, M Niceta, A Torraco, M Bianchi, M Santoro, A R Bentivoglio, E Bertini, F Piemonte, R Carrozzo, G. Silvestri

Research output: Contribution to journalArticle

Abstract

DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

Original languageEnglish
JournalClinical Genetics
DOIs
Publication statusE-pub ahead of print - Oct 6 2016

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Oxidative Stress
Biological Phenomena
Spinal Muscular Atrophy
Mutation
Parkinsonian Disorders
Deafness
Cataract
Parkinson Disease
Mitochondria
Fibroblasts
Adenosine Triphosphate
Biomarkers
Proteins

Keywords

  • Journal Article

Cite this

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title = "DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7",
abstract = "DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2{\%} of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.",
keywords = "Journal Article",
author = "{Di Nottia}, Michela and M Masciullo and D Verrigni and S Petrillo and A. Modoni and V Rizzo and {Di Giuda}, D. and T Rizza and M Niceta and A Torraco and M Bianchi and M Santoro and Bentivoglio, {A R} and E Bertini and F Piemonte and R Carrozzo and G. Silvestri",
note = "{\circledC} 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2016",
month = "10",
day = "6",
doi = "10.1111/cge.12841",
language = "English",
journal = "Clinical Genetics",
issn = "0009-9163",
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TY - JOUR

T1 - DJ-1 modulates mitochondrial response to oxidative stress

T2 - clues from a novel diagnosis of PARK7

AU - Di Nottia, Michela

AU - Masciullo, M

AU - Verrigni, D

AU - Petrillo, S

AU - Modoni, A.

AU - Rizzo, V

AU - Di Giuda, D.

AU - Rizza, T

AU - Niceta, M

AU - Torraco, A

AU - Bianchi, M

AU - Santoro, M

AU - Bentivoglio, A R

AU - Bertini, E

AU - Piemonte, F

AU - Carrozzo, R

AU - Silvestri, G.

N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2016/10/6

Y1 - 2016/10/6

N2 - DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

AB - DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c.461C>A [p.T154K] mutation in DJ-1. Patient's cultured fibroblasts showed low ATP synthesis, high ROS levels and reduced amount of some subunits of mitochondrial complex I; biomarkers of oxidative stress also resulted abnormal in patient's blood. The clinical pattern of multisystem involvement and the biochemical findings in our patient highlight the role for DJ-1 in modulating mitochondrial response against oxidative stress.

KW - Journal Article

U2 - 10.1111/cge.12841

DO - 10.1111/cge.12841

M3 - Article

C2 - 27460976

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

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