PMID- 30157433
OWN - NLM
STAT- MEDLINE
DCOM- 20200127
LR  - 20210109
IS  - 2211-1247 (Electronic)
VI  - 24
IP  - 9
DP  - 2018 Aug 28
TI  - Mitochondrial Complex I Activity Is Required for Maximal Autophagy.
PG  - 2404-2417.e8
LID - S2211-1247(18)31234-8 [pii]
LID - 10.1016/j.celrep.2018.07.101 [doi]
AB  - Cells adapt to nutrient and energy deprivation by inducing autophagy, which is 
      regulated by the mammalian target of rapamycin (mTOR) and AMP-activated protein 
      kinases (AMPKs). We found that cell metabolism significantly influences the 
      ability to induce autophagy, with mitochondrial complex I function being an 
      important factor in the initiation, amplitude, and duration of the response. We 
      show that phenformin or genetic defects in complex I suppressed autophagy induced 
      by mTOR inhibitors, whereas autophagy was enhanced by strategies that increased 
      mitochondrial metabolism. We report that mTOR inhibitors significantly increased 
      select phospholipids and mitochondrial-associated membranes (MAMs) in a complex 
      I-dependent manner. We attribute the complex I autophagy defect to the inability 
      to increase MAMs, limiting phosphatidylserine decarboxylase (PISD) activity and 
      mitochondrial phosphatidylethanolamine (mtPE), which support autophagy. Our data 
      reveal the dynamic and metabolic regulation of autophagy.
CI  - Published by Elsevier Inc.
FAU - Thomas, Hala Elnakat
AU  - Thomas HE
AD  - Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA.
FAU - Stefely, Jonathan A
AU  - Stefely JA
AD  - Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA; 
      Medical Scientist Training Program, School of Medicine and Public Health, 
      University of Wisconsin-Madison, Madison, WI, USA.
FAU - Veiga, Sonia R
AU  - Veiga SR
AD  - Laboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, 
      Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain.
FAU - Thomas, George
AU  - Thomas G
AD  - Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA; 
      Laboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, 
      Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain; Unit de 
      Biochemistry, Department of Physiological Sciences II, Faculty of Medicine, 
      Campus Universitari de Bellvitge-IDIBELL, University of Barcelona, 08908 
      L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
FAU - Kozma, Sara C
AU  - Kozma SC
AD  - Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA; 
      Laboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, 
      Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain.
FAU - Mercer, Carol A
AU  - Mercer CA
AD  - Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH, USA. 
      Electronic address: mercerc@ucmail.uc.edu.
LA  - eng
GR  - R21 CA191814/CA/NCI NIH HHS/United States
GR  - T32 GM008692/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Hypoglycemic Agents)
RN  - DD5K7529CE (Phenformin)
SB  - IM
MH  - Animals
MH  - Autophagy/*genetics
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Mitochondria/*metabolism
MH  - Phenformin/*pharmacology
PMC - PMC6298213
MID - NIHMS1505951
OTO - NOTNLM
OT  - AMPK
OT  - autophagy
OT  - mTOR
OT  - metabolism
OT  - mitochondria associated membrane
OT  - mitophagy
OT  - phenformin
OT  - phosphatidylethanolamine
OT  - phosphatidylserine decarboxylase
OT  - phospholipids
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2018/08/30 06:00
MHDA- 2020/01/28 06:00
PMCR- 2018/12/18
CRDT- 2018/08/30 06:00
PHST- 2017/12/04 00:00 [received]
PHST- 2018/04/17 00:00 [revised]
PHST- 2018/07/30 00:00 [accepted]
PHST- 2018/08/30 06:00 [entrez]
PHST- 2018/08/30 06:00 [pubmed]
PHST- 2020/01/28 06:00 [medline]
PHST- 2018/12/18 00:00 [pmc-release]
AID - S2211-1247(18)31234-8 [pii]
AID - 10.1016/j.celrep.2018.07.101 [doi]
PST - ppublish
SO  - Cell Rep. 2018 Aug 28;24(9):2404-2417.e8. doi: 10.1016/j.celrep.2018.07.101.