PMID- 37269467
OWN - NLM
STAT- MEDLINE
DCOM- 20230818
LR  - 20231213
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 238
IP  - 8
DP  - 2023 Aug
TI  - MitoNEET prevents iron overload-induced insulin resistance in H9c2 cells through 
      regulation of mitochondrial iron.
PG  - 1867-1875
LID - 10.1002/jcp.31044 [doi]
AB  - Iron overload (IO) induces insulin resistance in H9c2 cardiomyoblast cells. Here, 
      we used H9c2 cells overexpressing MitoNEET to examine the potential for 
      protection against iron accumulation in the mitochondria and subsequent insulin 
      resistance. In control H9c2 cells, IO was observed to increase mitochondrial iron 
      content, reactive oxygen species (ROS) production, mitochondrial fission, and 
      reduced insulin-stimulated Akt and ERK1/2 phosphorylation. IO did not 
      significantly affect mitophagy, or mitochondrial content, however, an increase in 
      peroxisome-proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha) 
      protein expression, a key regulator of mitochondrial biogenesis, was observed. 
      MitoNEET overexpression was able to attenuate the effects of IO on mitochondrial 
      iron content, reactive oxygen species, mitochondrial fission, and insulin 
      signaling. MitoNEET overexpression also upregulated levels of PGC1alpha protein. The 
      mitochondria-targeted antioxidant, Skq1, prevented IO-induced ROS production and 
      insulin resistance in control cells, indicating mitochondrial ROS plays a causal 
      role in the onset of insulin resistance. The selective mitochondrial fission 
      inhibitor, Mdivi-1, prevented IO-induced mitochondrial fission, however, it did 
      not alleviate IO-induced insulin resistance. Collectively, IO causes insulin 
      resistance in H9c2 cardiomyoblasts and this can be averted by reduction of 
      mitochondrial iron accumulation and ROS production by overexpression of the 
      MitoNEET protein.
CI  - (c) 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals 
      LLC.
FAU - Tam, Eddie
AU  - Tam E
AD  - Department of Biology, York University, Toronto, Ontario, Canada.
FAU - Sung, Hye K
AU  - Sung HK
AUID- ORCID: 0000-0002-4674-3796
AD  - Department of Biology, York University, Toronto, Ontario, Canada.
FAU - Sweeney, Gary
AU  - Sweeney G
AD  - Department of Biology, York University, Toronto, Ontario, Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230603
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Insulin)
RN  - E1UOL152H7 (Iron)
RN  - 0 (3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (mitochondrial protein 17 kDa, rat)
SB  - IM
MH  - Humans
MH  - Insulin/metabolism
MH  - *Insulin Resistance
MH  - Iron/metabolism
MH  - *Iron Overload/metabolism
MH  - Mitochondria/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 
      1-alpha/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - MitoNEET
OT  - Mitochondria
OT  - insulin resistance
OT  - iron overload
OT  - reactive oxygen species
EDAT- 2023/06/03 21:08
MHDA- 2023/08/17 06:43
CRDT- 2023/06/03 15:00
PHST- 2023/04/22 00:00 [revised]
PHST- 2023/02/11 00:00 [received]
PHST- 2023/05/06 00:00 [accepted]
PHST- 2023/08/17 06:43 [medline]
PHST- 2023/06/03 21:08 [pubmed]
PHST- 2023/06/03 15:00 [entrez]
AID - 10.1002/jcp.31044 [doi]
PST - ppublish
SO  - J Cell Physiol. 2023 Aug;238(8):1867-1875. doi: 10.1002/jcp.31044. Epub 2023 Jun 
      3.