PMID- 29729355
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20210109
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 678
DP  - 2018 Jun 21
TI  - Insertion of proteolipid protein into mitochondria but not DM20 regulates 
      metabolism of cells.
PG  - 90-98
LID - S0304-3940(18)30332-X [pii]
LID - 10.1016/j.neulet.2018.05.005 [doi]
AB  - Proteolipid protein (PLP), besides its adhesive role in myelin, has been 
      postulated to have multiple cellular functions. One well-documented function of 
      PLP is regulation of oligodendrocyte (Olg) apoptosis. In contrast, DM20, an 
      alternatively spliced product of the PLP1/Plp1 gene, has been proposed to have 
      functions that are unique from PLP but these functions have never been 
      elucidated. Here, we compare metabolism of PLP and DM20, and show that oxidative 
      phosphorylation (OxPhos) was significantly decreased in Plp1 but not DM20 or EGFP 
      expressing cells. The reserve OxPhos capacity of Plp1 expressing cells was half 
      of control cells, suggesting that they are very vulnerable to stress. ATP in 
      media of Plp1 expressing cells is significantly increased more than two-fold 
      compared to controls; markers of apoptosis are increased in cells over-expressing 
      Plp1, indicating that abnormal metabolism of PLP is most likely the direct cause 
      leading to Olg apoptosis. We hypothesize that abnormal metabolism, mediated by 
      increased insertion of PLP into mitochondria, underlies demyelination in 
      Pelizaeus-Merzbacher Disease (PMD) and in models of PMD. To understand why PLP 
      and DM20 function differently, we mutated or deleted amino acids located in the 
      PLP-specific region. All these mutations and deletions of the PLP-specific region 
      prevented insertion of PLP into mitochondria. These findings demonstrate that the 
      PLP-specific region is essential for PLP's import into mitochondria, and now 
      offer an explanation for deciphering unique functions of PLP and DM20.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Somayajulu, Mallika
AU  - Somayajulu M
AD  - Wayne State University School of Medicine Department of Anatomy and Cell Biology, 
      Detroit, MI, 48201, USA; Wayne State University School of Medicine Center for 
      Molecular Medicine and Genetics, Detroit, MI, 48201, USA.
FAU - Bessert, Denise A
AU  - Bessert DA
AD  - Wayne State University School of Medicine Department of Anatomy and Cell Biology, 
      Detroit, MI, 48201, USA.
FAU - Huttemann, Maik
AU  - Huttemann M
AD  - Wayne State University School of Medicine Center for Molecular Medicine and 
      Genetics, Detroit, MI, 48201, USA.
FAU - Sohi, Jasloveleen
AU  - Sohi J
AD  - University of Windsor Department of Chemistry, ON, Canada.
FAU - Kamholz, John
AU  - Kamholz J
AD  - University of Iowa, Des Moines IA, USA.
FAU - Skoff, Robert P
AU  - Skoff RP
AD  - Wayne State University School of Medicine Department of Anatomy and Cell Biology, 
      Detroit, MI, 48201, USA. Electronic address: rskoff@med.wayne.edu.
LA  - eng
GR  - R01 NS038236/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180502
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Myelin Proteolipid Protein)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Apoptosis
MH  - COS Cells
MH  - Cell Respiration
MH  - Chlorocebus aethiops
MH  - Lactic Acid/metabolism
MH  - Mitochondria/*metabolism
MH  - Mitochondrial Proteins/*metabolism
MH  - Myelin Proteolipid Protein/*metabolism
MH  - Pelizaeus-Merzbacher Disease/metabolism
PMC - PMC5975245
MID - NIHMS968113
OTO - NOTNLM
OT  - Metabolism
OT  - Mitochondria
OT  - Myelin
OT  - Oligodendrocytes
OT  - Pelizaeus-Merzbacher Disease
OT  - Proteolipid protein
EDAT- 2018/05/08 06:00
MHDA- 2019/04/16 06:00
PMCR- 2019/06/21
CRDT- 2018/05/06 06:00
PHST- 2018/02/15 00:00 [received]
PHST- 2018/04/18 00:00 [revised]
PHST- 2018/05/01 00:00 [accepted]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
PHST- 2018/05/06 06:00 [entrez]
PHST- 2019/06/21 00:00 [pmc-release]
AID - S0304-3940(18)30332-X [pii]
AID - 10.1016/j.neulet.2018.05.005 [doi]
PST - ppublish
SO  - Neurosci Lett. 2018 Jun 21;678:90-98. doi: 10.1016/j.neulet.2018.05.005. Epub 
      2018 May 2.