PMID- 38280232
OWN - NLM
STAT- MEDLINE
DCOM- 20240422
LR  - 20240422
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 33
IP  - 9
DP  - 2024 Apr 18
TI  - OPA1 mutation affects autophagy and triggers senescence in autosomal dominant 
      optic atrophy plus fibroblasts.
PG  - 768-786
LID - 10.1093/hmg/ddae008 [doi]
AB  - In several cases of mitochondrial diseases, the underlying genetic and 
      bioenergetic causes of reduced oxidative phosphorylation (OxPhos) in 
      mitochondrial dysfunction are well understood. However, there is still limited 
      knowledge about the specific cellular outcomes and factors involved for each gene 
      and mutation, which contributes to the lack of effective treatments for these 
      disorders. This study focused on fibroblasts from a patient with Autosomal 
      Dominant Optic Atrophy (ADOA) plus syndrome harboring a mutation in the Optic 
      Atrophy 1 (OPA1) gene. By combining functional and transcriptomic approaches, we 
      investigated the mitochondrial function and identified cellular phenotypes 
      associated with the disease. Our findings revealed that fibroblasts with the OPA1 
      mutation exhibited a disrupted mitochondrial network and function, leading to 
      altered mitochondrial dynamics and reduced autophagic response. Additionally, we 
      observed a premature senescence phenotype in these cells, suggesting a previously 
      unexplored role of the OPA1 gene in inducing senescence in ADOA plus patients. 
      This study provides novel insights into the mechanisms underlying mitochondrial 
      dysfunction in ADOA plus and highlights the potential importance of senescence in 
      disease progression.
CI  - (c) The Author(s) 2024. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Zanfardino, Paola
AU  - Zanfardino P
AD  - Department of Translational Biomedicine and Neuroscience (DiBraiN), University of 
      study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari, Italy.
FAU - Amati, Alessandro
AU  - Amati A
AD  - Department of Translational Biomedicine and Neuroscience (DiBraiN), University of 
      study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari, Italy.
FAU - Doccini, Stefano
AU  - Doccini S
AD  - Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS 
      Stella Maris Foundation, Viale del Tirreno, 56128 Calambrone, Pisa, Italy.
FAU - Cox, Sharon N
AU  - Cox SN
AD  - Department of Biosciences, Biotechnology, and Biopharmaceutics, University of 
      study of Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
FAU - Tullo, Apollonia
AU  - Tullo A
AD  - Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 
      National Research Council, Via G. Amendola 122/O, 70126 Bari, Italy.
FAU - Longo, Giovanna
AU  - Longo G
AD  - Department of Translational Biomedicine and Neuroscience (DiBraiN), University of 
      study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari, Italy.
FAU - D'Erchia, Annamaria
AU  - D'Erchia A
AD  - Department of Biosciences, Biotechnology, and Biopharmaceutics, University of 
      study of Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
FAU - Picardi, Ernesto
AU  - Picardi E
AUID- ORCID: 0000-0002-6549-0114
AD  - Department of Biosciences, Biotechnology, and Biopharmaceutics, University of 
      study of Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
FAU - Nesti, Claudia
AU  - Nesti C
AUID- ORCID: 0000-0001-5769-8655
AD  - Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS 
      Stella Maris Foundation, Viale del Tirreno, 56128 Calambrone, Pisa, Italy.
FAU - Santorelli, Filippo M
AU  - Santorelli FM
AUID- ORCID: 0000-0002-1359-9062
AD  - Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS 
      Stella Maris Foundation, Viale del Tirreno, 56128 Calambrone, Pisa, Italy.
FAU - Petruzzella, Vittoria
AU  - Petruzzella V
AUID- ORCID: 0000-0001-8771-6033
AD  - Department of Translational Biomedicine and Neuroscience (DiBraiN), University of 
      study of Bari Aldo Moro, Piazza G. Cesare, 11, 70124 Bari, Italy.
LA  - eng
GR  - 246-10 2019/REGIONE PUGLIA-MALATTIE RARE-Petruzzella/
GR  - Fondazione Opera Pia Monte di Pieta e Confidenze, Molfetta/
GR  - Italian Ministry of Health-Ricerca Corrente 2021/
PT  - Journal Article
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - EC 3.6.1.- (OPA1 protein, human)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
SB  - IM
MH  - Humans
MH  - *Optic Atrophy, Autosomal Dominant/genetics
MH  - *Mitochondrial Diseases
MH  - Mutation
MH  - Autophagy/genetics
MH  - Fibroblasts
MH  - GTP Phosphohydrolases/genetics
OTO - NOTNLM
OT  - ADOA plus
OT  - Autophagy
OT  - OPA1
OT  - mitochondria
OT  - mitophagy
OT  - senescence
EDAT- 2024/01/28 07:44
MHDA- 2024/04/22 06:45
CRDT- 2024/01/27 18:04
PHST- 2023/11/02 00:00 [received]
PHST- 2024/01/06 00:00 [revised]
PHST- 2024/01/08 00:00 [revised]
PHST- 2024/04/22 06:45 [medline]
PHST- 2024/01/28 07:44 [pubmed]
PHST- 2024/01/27 18:04 [entrez]
AID - 7590690 [pii]
AID - 10.1093/hmg/ddae008 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2024 Apr 18;33(9):768-786. doi: 10.1093/hmg/ddae008.