PMID- 37047537
OWN - NLM
STAT- MEDLINE
DCOM- 20230417
LR  - 20230417
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 7
DP  - 2023 Mar 31
TI  - Altered Mitochondrial Dynamic in Lymphoblasts and Fibroblasts Mutated for FANCA-A 
      Gene: The Central Role of DRP1.
LID - 10.3390/ijms24076557 [doi]
LID - 6557
AB  - Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow 
      failure and aplastic anemia. So far, 23 genes are involved in this pathology, and 
      their mutations lead to a defect in DNA repair. In recent years, it has been 
      observed that FA cells also display mitochondrial metabolism defects, causing an 
      accumulation of intracellular lipids and oxidative damage. However, the molecular 
      mechanisms involved in the metabolic alterations have not yet been elucidated. In 
      this work, by using lymphoblasts and fibroblasts mutated for the FANC-A gene, 
      oxidative phosphorylation (OxPhos) and mitochondria dynamics markers expression 
      was analyzed. Results show that the metabolic defect does not depend on an 
      altered expression of the proteins involved in OxPhos. However, FA cells are 
      characterized by increased uncoupling protein UCP2 expression. FANC-A mutation is 
      also associated with DRP1 overexpression that causes an imbalance in the 
      mitochondrial dynamic toward fission and lower expression of Parkin and Beclin1. 
      Treatment with P110, a specific inhibitor of DRP1, shows a partial mitochondrial 
      function recovery and the decrement of DRP1 and UCP2 expression, suggesting a 
      pivotal role of the mitochondrial dynamics in the etiopathology of Fanconi 
      anemia.
FAU - Bertola, Nadia
AU  - Bertola N
AUID- ORCID: 0000-0003-4591-3260
AD  - Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 
      Genova, Italy.
FAU - Bruno, Silvia
AU  - Bruno S
AD  - Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 
      Genova, Italy.
FAU - Capanni, Cristina
AU  - Capanni C
AD  - CNR Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza", Unit of Bologna, 
      Via di Barbiano 1/10, 40136 Bologna, Italy.
AD  - IRCCS Rizzoli Orthopedic Institute, Via Pupilli 1, 40136 Bologna, Italy.
FAU - Columbaro, Marta
AU  - Columbaro M
AD  - Electron Microscopy Platform, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, 
      Italy.
FAU - Mazzarello, Andrea Nicola
AU  - Mazzarello AN
AUID- ORCID: 0000-0003-2167-8817
AD  - Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 
      Genova, Italy.
FAU - Corsolini, Fabio
AU  - Corsolini F
AD  - Laboratory for the Study of Inborn Errors of Metabolism-Pediatric Clinic and 
      Endocrinology IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16148 
      Genova, Italy.
FAU - Regis, Stefano
AU  - Regis S
AUID- ORCID: 0000-0002-7723-2294
AD  - Laboratory of Clinical and Experimental Immunology, IRCCS Istituto Giannina 
      Gaslini, 16147 Genova, Italy.
FAU - Degan, Paolo
AU  - Degan P
AD  - U.O. Mutagenesis, IRCCS AOU San Martino-IST (Istituto Nazionale per la Ricerca 
      sul Cancro), Largo Rosanna Benzi 10, 16132 Genova, Italy.
FAU - Cappelli, Enrico
AU  - Cappelli E
AD  - Hematology Unit, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16148 
      Genova, Italy.
FAU - Ravera, Silvia
AU  - Ravera S
AUID- ORCID: 0000-0002-0803-1042
AD  - Department of Experimental Medicine, University of Genoa, Via De Toni 14, 16132 
      Genova, Italy.
LA  - eng
PT  - Journal Article
DEP - 20230331
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (FANCA protein, human)
RN  - 0 (Fanconi Anemia Complementation Group A Protein)
RN  - 0 (Proteins)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - Humans
MH  - *Fanconi Anemia/metabolism
MH  - Fanconi Anemia Complementation Group A Protein/genetics/metabolism
MH  - Fibroblasts/metabolism
MH  - Mitochondria/metabolism
MH  - *Mitochondrial Dynamics/genetics
MH  - Proteins/metabolism
MH  - Dynamins/metabolism
PMC - PMC10094900
OTO - NOTNLM
OT  - Fanconi anemia
OT  - OxPhos
OT  - aerobic metabolism
OT  - fission
OT  - fusion
OT  - mitochondrial dynamics
COIS- The authors declare no conflict of interest.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/14 06:41
PMCR- 2023/03/31
CRDT- 2023/04/13 01:12
PHST- 2022/12/19 00:00 [received]
PHST- 2023/03/02 00:00 [revised]
PHST- 2023/03/21 00:00 [accepted]
PHST- 2023/04/14 06:41 [medline]
PHST- 2023/04/13 01:12 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/03/31 00:00 [pmc-release]
AID - ijms24076557 [pii]
AID - ijms-24-06557 [pii]
AID - 10.3390/ijms24076557 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Mar 31;24(7):6557. doi: 10.3390/ijms24076557.