PMID- 24930972
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20221222
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 20
IP  - 2
DP  - 2014 Aug 5
TI  - Lipin-1 regulates autophagy clearance and intersects with statin drug effects in 
      skeletal muscle.
PG  - 267-79
LID - S1550-4131(14)00211-3 [pii]
LID - 10.1016/j.cmet.2014.05.003 [doi]
AB  - LPIN1 encodes lipin-1, a phosphatidic acid phosphatase (PAP) enzyme that 
      catalyzes the dephosphorylation of phosphatidic acid to form diacylglycerol. 
      Homozygous LPIN1 gene mutations cause severe rhabdomyolysis, and heterozygous 
      LPIN1 missense mutations may promote statin-induced myopathy. We demonstrate that 
      lipin-1-related myopathy in the mouse is associated with a blockade in autophagic 
      flux and accumulation of aberrant mitochondria. Lipin-1 PAP activity is required 
      for maturation of autolysosomes, through its activation of the protein kinase D 
      (PKD)-Vps34 phosphatidylinositol 3-kinase signaling cascade. Statin treatment 
      also reduces PKD activation and autophagic flux, which are compounded by 
      diminished mammalian target of rapamycin (mTOR) abundance in 
      lipin-1-haploinsufficent and -deficient muscle. Lipin-1 restoration in skeletal 
      muscle prevents myonecrosis and statin toxicity in vivo, and activated PKD 
      rescues autophagic flux in lipin-1-deficient cells. Our findings identify lipin-1 
      PAP activity as a component of the macroautophagy pathway and define the basis 
      for lipin-1-related myopathies.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Zhang, Peixiang
AU  - Zhang P
AD  - Department of Human Genetics, David Geffen School of Medicine at UCLA, Los 
      Angeles, CA 90095, USA.
FAU - Verity, M Anthony
AU  - Verity MA
AD  - Division of Neuropathology, Department of Pathology and Laboratory Medicine, 
      David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
FAU - Reue, Karen
AU  - Reue K
AD  - Department of Human Genetics, David Geffen School of Medicine at UCLA, Los 
      Angeles, CA 90095, USA; Department of Medicine, David Geffen School of Medicine 
      at UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: 
      reuek@ucla.edu.
LA  - eng
GR  - S10RR026744/RR/NCRR NIH HHS/United States
GR  - R01 HL102661/HL/NHLBI NIH HHS/United States
GR  - P20 RR016475/RR/NCRR NIH HHS/United States
GR  - P20RR16475/RR/NCRR NIH HHS/United States
GR  - S10 RR026744/RR/NCRR NIH HHS/United States
GR  - P20 GM103418/GM/NIGMS NIH HHS/United States
GR  - P01 HL090553/HL/NHLBI NIH HHS/United States
GR  - P01 HL028481/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000124/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140612
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Lipids)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nuclear Proteins)
RN  - EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.- (protein kinase D)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - EC 3.1.3.4 (Lpin1 protein, mouse)
RN  - EC 3.1.3.4 (Phosphatidate Phosphatase)
SB  - IM
CIN - Cell Cycle. 2014;13(24):3789-90. PMID: 25483058
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Line
MH  - Class III Phosphatidylinositol 3-Kinases/metabolism
MH  - Creatine Kinase/blood
MH  - Female
MH  - Haploinsufficiency/drug effects
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Lipids/analysis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microtubule-Associated Proteins/metabolism
MH  - Mitochondria/metabolism
MH  - Muscle, Skeletal/drug effects/metabolism/pathology
MH  - Nuclear Proteins/deficiency/genetics/*metabolism
MH  - Phosphatidate Phosphatase/deficiency/genetics/*metabolism
MH  - Protein Kinase C/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC4170588
MID - NIHMS599053
EDAT- 2014/06/17 06:00
MHDA- 2015/03/31 06:00
PMCR- 2015/08/05
CRDT- 2014/06/17 06:00
PHST- 2013/12/03 00:00 [received]
PHST- 2014/03/03 00:00 [revised]
PHST- 2014/04/21 00:00 [accepted]
PHST- 2014/06/17 06:00 [entrez]
PHST- 2014/06/17 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2015/08/05 00:00 [pmc-release]
AID - S1550-4131(14)00211-3 [pii]
AID - 10.1016/j.cmet.2014.05.003 [doi]
PST - ppublish
SO  - Cell Metab. 2014 Aug 5;20(2):267-79. doi: 10.1016/j.cmet.2014.05.003. Epub 2014 
      Jun 12.