PMID- 28283188
OWN - NLM
STAT- MEDLINE
DCOM- 20171208
LR  - 20211204
IS  - 1873-135X (Electronic)
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 806
DP  - 2017 Dec
TI  - Targeted cytoplasmic irradiation and autophagy.
PG  - 88-97
LID - S0027-5107(16)30147-6 [pii]
LID - 10.1016/j.mrfmmm.2017.02.004 [doi]
AB  - The effect of ionizing irradiation on cytoplasmic organelles is often 
      underestimated because the general dogma considers direct DNA damage in the 
      nuclei to be the primary cause of radiation induced toxicity. Using a precision 
      microbeam irradiator, we examined the changes in mitochondrial dynamics and 
      functions triggered by targeted cytoplasmic irradiation with alpha-particles. 
      Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to 
      activation of autophagy, which degraded dysfunctional mitochondria in order to 
      maintain cellular energy homeostasis. The activation of autophagy was cytoplasmic 
      irradiation-specific and was not detected in nuclear irradiated cells. This 
      autophagic process was oxyradical-dependent and required the activity of the 
      mitochondrial fission protein dynamin related protein 1 (DRP1). The resultant 
      mitochondrial fission induced phosphorylation of AMP activated protein kinase 
      (AMPK) which leads to further activation of the extracellular signal-related 
      kinase (ERK) 1/2 with concomitant inhibition of the mammalian target of rapamycin 
      (mTOR) to initiate autophagy. Inhibition of autophagy resulted in delayed DNA 
      damage repair and decreased cell viability, which supports the cytoprotective 
      function of autophagy. Our results reveal a novel mechanism in which 
      dysfunctional mitochondria are degraded by autophagy in an attempt to protect 
      cells from toxic effects of targeted cytoplasmic radiation.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Wu, Jinhua
AU  - Wu J
AD  - Center for Radiological Research, College of Physicians and Surgeons, Columbia 
      University, 630 West 168th Street, VC 11-205, New York, N.Y., United States; 
      Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui, 230031, 
      China.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Center for Radiological Research, College of Physicians and Surgeons, Columbia 
      University, 630 West 168th Street, VC 11-205, New York, N.Y., United States.
FAU - Wuu, Yen-Ruh
AU  - Wuu YR
AD  - Center for Radiological Research, College of Physicians and Surgeons, Columbia 
      University, 630 West 168th Street, VC 11-205, New York, N.Y., United States.
FAU - Davidson, Mercy M
AU  - Davidson MM
AD  - Department of Radiation Oncology, Columbia University, 630 West 168th Street, P&S 
      11-451, New York, N.Y., 10032, United States.
FAU - Hei, Tom K
AU  - Hei TK
AD  - Center for Radiological Research, College of Physicians and Surgeons, Columbia 
      University, 630 West 168th Street, VC 11-205, New York, N.Y., United States. 
      Electronic address: tkh1@cumc.columbia.edu.
LA  - eng
GR  - P01 CA049062/CA/NCI NIH HHS/United States
GR  - P41 EB002033/EB/NIBIB NIH HHS/United States
GR  - R01 ES012888/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20170301
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Alpha Particles
MH  - Apoptosis/*radiation effects
MH  - Autophagy/*radiation effects
MH  - Cells, Cultured
MH  - Cytoplasm/*radiation effects
MH  - Epithelial Cells/*pathology/radiation effects
MH  - Humans
MH  - Mitochondrial Dynamics
MH  - Reactive Oxygen Species/metabolism
MH  - Respiratory System/*pathology/radiation effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5581273
MID - NIHMS858992
OTO - NOTNLM
OT  - AMPK
OT  - Autophagy
OT  - Cytoplasmic irradiation
OT  - DRP1
OT  - Mitochondria dysfunction
OT  - Mitophagy
EDAT- 2017/03/12 06:00
MHDA- 2017/12/09 06:00
PMCR- 2018/12/01
CRDT- 2017/03/12 06:00
PHST- 2016/09/08 00:00 [received]
PHST- 2017/02/27 00:00 [revised]
PHST- 2017/02/27 00:00 [accepted]
PHST- 2017/03/12 06:00 [pubmed]
PHST- 2017/12/09 06:00 [medline]
PHST- 2017/03/12 06:00 [entrez]
PHST- 2018/12/01 00:00 [pmc-release]
AID - S0027-5107(16)30147-6 [pii]
AID - 10.1016/j.mrfmmm.2017.02.004 [doi]
PST - ppublish
SO  - Mutat Res. 2017 Dec;806:88-97. doi: 10.1016/j.mrfmmm.2017.02.004. Epub 2017 Mar 
      1.