PMID- 32411091
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20210526
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 11
DP  - 2020
TI  - MiD51 Is Important for Maintaining Mitochondrial Health in Pancreatic Islet and 
      MIN6 Cells.
PG  - 232
LID - 10.3389/fendo.2020.00232 [doi]
LID - 232
AB  - Background: Mitochondrial dynamics are important for glucose-stimulated insulin 
      secretion in pancreatic beta cells. The mitochondrial elongation factor MiD51 has 
      been proposed to act as an anchor that recruits Drp1 from the cytosol to the 
      outer mitochondrial membrane. Whether MiD51 promotes mitochondrial fusion by 
      inactivation of Drp1 is a controversial issue. Since both the underlying 
      mechanism and the effects on mitochondrial function remain unknown, this study 
      was conducted to investigate the role of MiD51 in beta cells. Methods: 
      Overexpression and downregulation of MiD51 in mouse insulinoma 6 (MIN6) and mouse 
      islet cells was achieved using the pcDNA expression vector and specific siRNA, 
      respectively. Expression of genes regulating mitochondrial dynamics and autophagy 
      was analyzed by quantitative Real-Time PCR, glucose-stimulated insulin secretion 
      by ELISA, and cellular oxygen consumption rate by optode sensor technology. 
      Mitochondrial membrane potential and morphology were visualized after TMRE and 
      MitoTracker Green staining, respectively. Immunofluorescence analyses were 
      examined by confocal microscopy. Results: MiD51 is expressed in insulin-positive 
      mouse and human pancreatic islet and MIN6 cells. Overexpression of MiD51 resulted 
      in mitochondrial fragmentation and cluster formation in MIN6 cells. Mitochondrial 
      membrane potential, glucose-induced oxygen consumption rate and 
      glucose-stimulated insulin secretion were reduced in MIN6 cells with high MiD51 
      expression. LC3 expression remained unchanged. Downregulation of MiD51 resulted 
      in inhomogeneity of the mitochondrial network in MIN6 cells with hyperelongated 
      and fragmented mitochondria. Mitochondrial membrane potential, maximal and 
      glucose-induced oxygen consumption rate and insulin secretion were diminished in 
      MIN6 cells with low MiD51 expression. Furthermore, reduced Mfn2 and Parkin 
      expression was observed. Based on MiD51 overexpression and downregulation, 
      changes in the mitochondrial network structure similar to those in MIN6 cells 
      were also observed in mouse islet cells. Conclusion: We have demonstrated that 
      MiD51 plays a pivotal role in regulating mitochondrial function and hence insulin 
      secretion in MIN6 cells. We propose that this anchor protein of Drp1 is important 
      to maintain a homogeneous mitochondrial network and to avoid morphologies such as 
      hyperelongation and clustering which are inaccessible for degradation by 
      autophagy. Assuming that insulin granule degradation frequently suppresses 
      autophagy in beta cells, MiD51 could be a key element maintaining mitochondrial 
      health.
CI  - Copyright (c) 2020 Schultz, Warkus, Wolke, Waterstradt and Baltrusch.
FAU - Schultz, Julia
AU  - Schultz J
AD  - Institute of Medical Biochemistry and Molecular Biology, University Medicine 
      Rostock, Rostock, Germany.
FAU - Warkus, Jeanette
AU  - Warkus J
AD  - Institute of Medical Biochemistry and Molecular Biology, University Medicine 
      Rostock, Rostock, Germany.
FAU - Wolke, Carmen
AU  - Wolke C
AD  - Institute of Medical Biochemistry and Molecular Biology, University Medicine 
      Greifswald, Greifswald, Germany.
FAU - Waterstradt, Rica
AU  - Waterstradt R
AD  - Institute of Medical Biochemistry and Molecular Biology, University Medicine 
      Rostock, Rostock, Germany.
FAU - Baltrusch, Simone
AU  - Baltrusch S
AD  - Institute of Medical Biochemistry and Molecular Biology, University Medicine 
      Rostock, Rostock, Germany.
AD  - Department Life, Light & Matter, University of Rostock, Rostock, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200428
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Insulin)
RN  - 0 (MIEF1 protein, human)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Peptide Elongation Factors)
RN  - 0 (Zrf2 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulinoma/metabolism/*pathology
MH  - Islets of Langerhans/cytology/*physiology
MH  - Mice
MH  - Mitochondria/*physiology
MH  - Mitochondrial Dynamics
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Pancreatic Neoplasms/metabolism/*pathology
MH  - Peptide Elongation Factors/genetics/*metabolism
PMC - PMC7198722
OTO - NOTNLM
OT  - MiD51
OT  - mitochondrial dynamics
OT  - mitochondrial fission
OT  - mitophagy
OT  - pancreatic beta cells
EDAT- 2020/05/16 06:00
MHDA- 2021/05/27 06:00
PMCR- 2020/01/01
CRDT- 2020/05/16 06:00
PHST- 2020/01/26 00:00 [received]
PHST- 2020/03/31 00:00 [accepted]
PHST- 2020/05/16 06:00 [entrez]
PHST- 2020/05/16 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2020.00232 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2020 Apr 28;11:232. doi: 10.3389/fendo.2020.00232. 
      eCollection 2020.