PMID- 35406757
OWN - NLM
STAT- MEDLINE
DCOM- 20220413
LR  - 20230222
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 7
DP  - 2022 Apr 1
TI  - Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal 
      Hypoxia-Ischemia.
LID - 10.3390/cells11071193 [doi]
LID - 1193
AB  - Hypoxia-ischemia (HI) leads to immature brain injury mediated by mitochondrial 
      stress. If damaged mitochondria cannot be repaired, mitochondrial 
      permeabilization ensues, leading to cell death. Non-optimal turnover of 
      mitochondria is critical as it affects short and long term structural and 
      functional recovery and brain development. Therefore, disposal of deficient 
      mitochondria via mitophagy and their replacement through biogenesis is needed. We 
      utilized mt-Keima reporter mice to quantify mitochondrial morphology (fission, 
      fusion) and mitophagy and their mechanisms in primary neurons after Oxygen 
      Glucose Deprivation (OGD) and in brain sections after neonatal HI. Molecular 
      mechanisms of PARK2-dependent and -independent pathways of mitophagy were 
      investigated in vivo by PCR and Western blotting. Mitochondrial morphology and 
      mitophagy were investigated using live cell microscopy. In primary neurons, we 
      found a primary fission wave immediately after OGD with a significant increase in 
      mitophagy followed by a secondary phase of fission at 24 h following recovery. 
      Following HI, mitophagy was upregulated immediately after HI followed by a second 
      wave at 7 days. Western blotting suggests that both PINK1/Parkin-dependent and 
      -independent mechanisms, including NIX and FUNDC1, were upregulated immediately 
      after HI, whereas a PINK1/Parkin mechanism predominated 7 days after HI. We 
      hypothesize that excessive mitophagy in the early phase is a pathologic response 
      which may contribute to secondary energy depletion, whereas secondary mitophagy 
      may be involved in post-HI regeneration and repair.
FAU - Nair, Syam
AU  - Nair S
AUID- ORCID: 0000-0001-8470-2162
AD  - Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
AD  - Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of 
      Gothenburg, 41390 Gothenburg, Sweden.
AD  - Institute of Clinical Sciences, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
FAU - Leverin, Anna-Lena
AU  - Leverin AL
AD  - Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
AD  - Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of 
      Gothenburg, 41390 Gothenburg, Sweden.
FAU - Rocha-Ferreira, Eridan
AU  - Rocha-Ferreira E
AUID- ORCID: 0000-0002-9342-4691
AD  - Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
AD  - Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of 
      Gothenburg, 41390 Gothenburg, Sweden.
AD  - Institute of Clinical Sciences, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
FAU - Sobotka, Kristina S
AU  - Sobotka KS
AD  - Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
AD  - Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of 
      Gothenburg, 41390 Gothenburg, Sweden.
FAU - Thornton, Claire
AU  - Thornton C
AUID- ORCID: 0000-0001-7676-3272
AD  - Department of Comparative Biomedical Sciences, Royal Veterinary College, London 
      NW1 0TU, UK.
FAU - Mallard, Carina
AU  - Mallard C
AUID- ORCID: 0000-0001-8953-919X
AD  - Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
AD  - Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of 
      Gothenburg, 41390 Gothenburg, Sweden.
FAU - Hagberg, Henrik
AU  - Hagberg H
AD  - Centre of Perinatal Medicine and Health, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
AD  - Institute of Clinical Sciences, The Sahlgrenska Academy, University of 
      Gothenburg, 41685 Gothenburg, Sweden.
LA  - eng
GR  - MR/T014725/1/MRC_/Medical Research Council/United Kingdom
GR  - WT094823/WT_/Wellcome Trust/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220401
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (FUNDC1 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Glucose
MH  - Hypoxia
MH  - Ischemia
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mitochondrial Proteins/metabolism
MH  - *Mitophagy/physiology
MH  - Protein Kinases/metabolism
MH  - *Ubiquitin-Protein Ligases/metabolism
PMC - PMC8997592
OTO - NOTNLM
OT  - metabolism
OT  - mitochondria
OT  - mitochondrial fission
OT  - mitophagy
OT  - neonatal brain injury
OT  - neonatal hypoxia-ischemia
OT  - reactive oxygen species
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/04/13 06:00
MHDA- 2022/04/14 06:00
PMCR- 2022/04/01
CRDT- 2022/04/12 01:05
PHST- 2021/12/20 00:00 [received]
PHST- 2022/03/25 00:00 [revised]
PHST- 2022/03/30 00:00 [accepted]
PHST- 2022/04/12 01:05 [entrez]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/04/14 06:00 [medline]
PHST- 2022/04/01 00:00 [pmc-release]
AID - cells11071193 [pii]
AID - cells-11-01193 [pii]
AID - 10.3390/cells11071193 [doi]
PST - epublish
SO  - Cells. 2022 Apr 1;11(7):1193. doi: 10.3390/cells11071193.