PMID- 28843778
OWN - NLM
STAT- MEDLINE
DCOM- 20180529
LR  - 20230903
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 112
DP  - 2017 Nov
TI  - Elimination of dysfunctional mitochondria through mitophagy suppresses 
      benzo[a]pyrene-induced apoptosis.
PG  - 452-463
LID - S0891-5849(17)30736-0 [pii]
LID - 10.1016/j.freeradbiomed.2017.08.020 [doi]
AB  - Mitophagy, a special type of autophagy, plays an important role in the 
      mitochondria quality control and cellular homeostasis. In this study, we examined 
      the molecular mechanism of mitophagy induction with benzo[a]pyrene (B[a]P), a 
      ubiquitous polycyclic aromatic hydrocarbon, which acts as a prosurvival response 
      against apoptotic cell death. Our study showed that B[a]P displayed higher 
      cytotoxicity in autophagy-deficient HaCaT cells as compared to control. Further, 
      we showed that B[a]P triggered the Beclin-1-dependent autophagy through the 
      mammalian target of rapamycin (mTOR)/AMP-activated protein kinase (AMPK) pathway. 
      Moreover, our study indicated that the B[a]P-induced autophagy was initiated 
      through the activation of cytochrome P450 1B1 (CYP1B1) and the aryl hydrocarbon 
      receptor (AhR) in HaCaT cells. Intriguingly, the B[a]P-induced Beclin-1-mediated 
      mitophagy was suppressed in CYP1B1 and AhR knockdown HaCaT cells, indicating a 
      crucial role of B[a]P activation in the mitophagy induction to regulate cell 
      death. B[a]P was shown to increase the mitochondrial dysfunction and decrease the 
      mitochondrial membrane potential, resulting in depletion of ATP level along with 
      the inhibition of the oxygen consumption rate in HaCaT cells. Importantly, the 
      supplementation of methyl pyruvate compensated for the B[a]P-induced drop in the 
      ATP level and mitigated the reactive oxygen species burden and autophagy. 
      Mechanistically, B[a]P inhibited the manganese superoxide dismutase (MnSOD) 
      activity and we found that the activated mitochondrial CYP1B1 interacted with 
      MnSOD, inflicting mitophagy to protect from B[a]P-induced apoptosis. In summary, 
      our study reveals mitophagy induction as a cellular protection mechanism against 
      B[a]P-triggered toxicity and carcinogenesis.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Das, Durgesh Nandini
AU  - Das DN
AD  - Department of Life Science, National Institute of Technology Rourkela, Rourkela 
      769008, Odisha, India.
FAU - Naik, Prajna Paramita
AU  - Naik PP
AD  - Department of Life Science, National Institute of Technology Rourkela, Rourkela 
      769008, Odisha, India.
FAU - Mukhopadhyay, Subhadip
AU  - Mukhopadhyay S
AD  - Department of Life Science, National Institute of Technology Rourkela, Rourkela 
      769008, Odisha, India.
FAU - Panda, Prashanta Kumar
AU  - Panda PK
AD  - Department of Life Science, National Institute of Technology Rourkela, Rourkela 
      769008, Odisha, India.
FAU - Sinha, Niharika
AU  - Sinha N
AD  - Department of Life Science, National Institute of Technology Rourkela, Rourkela 
      769008, Odisha, India.
FAU - Meher, Biswa Ranjan
AU  - Meher BR
AD  - Centre for Life Sciences, Central University of Jharkhand, Brambe, Ranchi 835205, 
      Jharkhand, India.
FAU - Bhutia, Sujit K
AU  - Bhutia SK
AD  - Department of Life Science, National Institute of Technology Rourkela, Rourkela 
      769008, Odisha, India. Electronic address: bhutiask@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20170824
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (AHR protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Beclin-1)
RN  - 0 (Carcinogens)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.14.14.1 (CYP1B1 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
EIN - Free Radic Biol Med. 2023 Nov 1;208:371. PMID: 37660591
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Adenosine Triphosphate/antagonists & inhibitors/biosynthesis
MH  - Apoptosis/*drug effects/genetics
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
MH  - Beclin-1/genetics/metabolism
MH  - Benzo(a)pyrene/*toxicity
MH  - Carcinogens/*toxicity
MH  - Cell Line, Transformed
MH  - Cytochrome P-450 CYP1B1/genetics/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Keratinocytes/*drug effects/metabolism/pathology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/*drug effects/metabolism/pathology
MH  - Mitophagy/*drug effects/genetics
MH  - Oxygen Consumption/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Aryl Hydrocarbon/genetics/metabolism
MH  - Superoxide Dismutase/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
OTO - NOTNLM
OT  - ATP depletion
OT  - Apoptosis
OT  - Benzo[a]pyrene
OT  - CYP1B1
OT  - Mitophagy
OT  - MnSOD
EDAT- 2017/08/28 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/08/28 06:00
PHST- 2017/03/06 00:00 [received]
PHST- 2017/08/20 00:00 [revised]
PHST- 2017/08/22 00:00 [accepted]
PHST- 2017/08/28 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/08/28 06:00 [entrez]
AID - S0891-5849(17)30736-0 [pii]
AID - 10.1016/j.freeradbiomed.2017.08.020 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2017 Nov;112:452-463. doi: 
      10.1016/j.freeradbiomed.2017.08.020. Epub 2017 Aug 24.