PMID- 31133888
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 10
DP  - 2019
TI  - Mitochondrial Dysfunction Is Inducible in Lymphoblastoid Cell Lines From Children 
      With Autism and May Involve the TORC1 Pathway.
PG  - 269
LID - 10.3389/fpsyt.2019.00269 [doi]
LID - 269
AB  - We previously developed a lymphoblastoid cell line (LCL) model of mitochondrial 
      dysfunction in autism spectrum disorder (ASD); some individuals with ASD showed 
      mitochondrial dysfunction (AD-A) while other individuals (AD-N) demonstrated 
      mitochondrial respiration similar to controls (CNT). To test the hypothesis that 
      mitochondrial dysfunction could be a consequence of environmental exposures 
      through chronic elevations in reactive oxygen species (ROS), we exposed LCLs to 
      prolonged ROS. We also examined expression of metabolic regulatory genes and the 
      modulating effect of the mechanistic target of rapamycin (mTOR) pathway. 
      Prolonged ROS exposure induced or worsened mitochondrial dysfunction in all LCL 
      groups. Expression of genes associated with ROS protection was elevated in both 
      AD-N and AD-A LCLs, but mitochondrial fission/fusion and mitoplasticity gene 
      expression was only increased in AD-N LCLs. Partial least squares discriminant 
      analysis showed that mTOR, UCP2 (uncoupling protein 2), SIRT1 (sirtuin 1), and 
      MFN2 (mitofusin-2) gene expression differentiated LCL groups. Low-dose rapamycin 
      (0.1 nM) normalized respiration with the magnitude of this normalization greater 
      for AD-A LCLs, suggesting that the mammalian target of rapamycin complex 1 
      (mTORC1) pathway may have a different dynamic range for regulating mitochondrial 
      activity in individuals with ASD with and without mitochondrial dysfunction, 
      potentially related to S6K1 (S6 kinase beta-1) regulation. Understanding pathways 
      that underlie mitochondrial dysfunction in ASD may lead to novel treatments.
FAU - Bennuri, Sirish C
AU  - Bennuri SC
AD  - Arkansas Children's Research Institute and Department of Pediatrics, University 
      of Arkansas for Medical Sciences, Little Rock, AR, United States.
FAU - Rose, Shannon
AU  - Rose S
AD  - Arkansas Children's Research Institute and Department of Pediatrics, University 
      of Arkansas for Medical Sciences, Little Rock, AR, United States.
FAU - Frye, Richard E
AU  - Frye RE
AD  - Barrow Neurologic Institute at Phoenix Children's Hospital, Phoenix, AZ, United 
      States.
AD  - Department of Child Health, University of Arizona College of Medicine-Phoenix, 
      Phoenix, AZ, United States.
LA  - eng
PT  - Journal Article
DEP - 20190507
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC6514096
OTO - NOTNLM
OT  - autism
OT  - mechanistic target of rapamycin
OT  - mitochondria
OT  - mitoplasticity
OT  - reactive oxygen species
EDAT- 2019/05/28 06:00
MHDA- 2019/05/28 06:01
PMCR- 2019/05/07
CRDT- 2019/05/29 06:00
PHST- 2018/12/21 00:00 [received]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/05/29 06:00 [entrez]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2019/05/28 06:01 [medline]
PHST- 2019/05/07 00:00 [pmc-release]
AID - 10.3389/fpsyt.2019.00269 [doi]
PST - epublish
SO  - Front Psychiatry. 2019 May 7;10:269. doi: 10.3389/fpsyt.2019.00269. eCollection 
      2019.