PMID- 32365535
OWN - NLM
STAT- MEDLINE
DCOM- 20210209
LR  - 20240328
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 9
DP  - 2020 Apr 29
TI  - Targeting Mitochondrial Network Architecture in Down Syndrome and Aging.
LID - 10.3390/ijms21093134 [doi]
LID - 3134
AB  - Mitochondria are organelles that mainly control energy conversion in the cell. In 
      addition, they also participate in many relevant activities, such as the 
      regulation of apoptosis and calcium levels, and other metabolic tasks, all 
      closely linked to cell viability. Functionality of mitochondria appears to depend 
      upon their network architecture that may dynamically pass from an interconnected 
      structure with long tubular units, to a fragmented one with short separate 
      fragments. A decline in mitochondrial quality, which presents itself as an 
      altered structural organization and a function of mitochondria, has been observed 
      in Down syndrome (DS), as well as in aging and in age-related pathologies. This 
      review provides a basic overview of mitochondrial dynamics, from fission/fusion 
      mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the 
      disruption of the mitochondrial phenotype in DS and aging are discussed. The 
      impaired activity of the transcriptional co-activator PGC-1alpha/PPARGC1A and the 
      hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging 
      as molecular underlying causes of these mitochondrial alterations. It is, 
      therefore, likely that either stimulating the PGC-1alpha activity or inhibiting mTOR 
      signaling could reverse mitochondrial dysfunction. Evidence is summarized 
      suggesting that drugs targeting either these pathways or other factors affecting 
      the mitochondrial network may represent therapeutic approaches to improve and/or 
      prevent the effects of altered mitochondrial function. Overall, from all these 
      studies it emerges that the implementation of such strategies may exert 
      protective effects in DS and age-related diseases.
FAU - Mollo, Nunzia
AU  - Mollo N
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Cicatiello, Rita
AU  - Cicatiello R
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Aurilia, Miriam
AU  - Aurilia M
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Scognamiglio, Roberta
AU  - Scognamiglio R
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Genesio, Rita
AU  - Genesio R
AUID- ORCID: 0000-0003-2640-7362
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Charalambous, Maria
AU  - Charalambous M
AD  - Institute of Experimental Endocrinology and Oncology "G. Salvatore", National 
      Research Council, 80131 Naples, Italy.
FAU - Paladino, Simona
AU  - Paladino S
AUID- ORCID: 0000-0001-5332-6774
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Conti, Anna
AU  - Conti A
AUID- ORCID: 0000-0002-2054-7375
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Nitsch, Lucio
AU  - Nitsch L
AUID- ORCID: 0000-0003-0672-3528
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
AD  - Institute of Experimental Endocrinology and Oncology "G. Salvatore", National 
      Research Council, 80131 Naples, Italy.
FAU - Izzo, Antonella
AU  - Izzo A
AD  - Department of Molecular Medicine and Medical Biotechnology, University of Naples 
      Federico II, 80131 Naples, Italy.
LA  - eng
GR  - POR Campania FSE 2007-2013 Project CREME/Regione Campania/
GR  - POR Campania FSE 2014-2020/Regione Campania/
GR  - Lejeune Project #1698/Fondation Jerome Lejeune/
PT  - Journal Article
PT  - Review
DEP - 20200429
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
SB  - IM
MH  - Aging/drug effects/genetics/*metabolism
MH  - Animals
MH  - Biomarkers
MH  - Disease Susceptibility
MH  - Down Syndrome/drug therapy/*etiology/*metabolism
MH  - Homeostasis
MH  - Humans
MH  - Mitochondria/drug effects/genetics/*metabolism/*ultrastructure
MH  - *Mitochondrial Dynamics/drug effects
MH  - Molecular Targeted Therapy
MH  - Signal Transduction/drug effects
PMC - PMC7247689
OTO - NOTNLM
OT  - Down syndrome
OT  - PGC-1alpha/PPARGC1A
OT  - aging
OT  - mTOR
OT  - mitochondrial dynamics
OT  - mitochondrial function
OT  - mitochondrial network
COIS- The authors declare no conflicts of interest.
EDAT- 2020/05/06 06:00
MHDA- 2021/02/10 06:00
PMCR- 2020/05/01
CRDT- 2020/05/06 06:00
PHST- 2020/04/09 00:00 [received]
PHST- 2020/04/26 00:00 [revised]
PHST- 2020/04/27 00:00 [accepted]
PHST- 2020/05/06 06:00 [entrez]
PHST- 2020/05/06 06:00 [pubmed]
PHST- 2021/02/10 06:00 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - ijms21093134 [pii]
AID - ijms-21-03134 [pii]
AID - 10.3390/ijms21093134 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Apr 29;21(9):3134. doi: 10.3390/ijms21093134.