PMID- 34063207
OWN - NLM
STAT- MEDLINE
DCOM- 20210622
LR  - 20210622
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 9
DP  - 2021 May 2
TI  - Mitochondrial Dysfunction in Podocytes Caused by CRIF1 Deficiency Leads to 
      Progressive Albuminuria and Glomerular Sclerosis in Mice.
LID - 10.3390/ijms22094827 [doi]
LID - 4827
AB  - Recent studies have implicated mitochondrial disruption in podocyte dysfunction, 
      which is a characteristic feature of primary and diabetic glomerular diseases. 
      However, the mechanisms by which primary mitochondrial dysfunction in podocytes 
      affects glomerular renal diseases are currently unknown. To investigate the role 
      of mitochondrial oxidative phosphorylation (OxPhos) in podocyte dysfunction, 
      glomerular function was examined in mice carrying a loss of function mutation of 
      the gene encoding CR6-interacting factor-1 (CRIF1), which is essential for 
      intramitochondrial production and the subsequent insertion of OxPhos polypeptides 
      into the inner mitochondrial membrane. Homozygotic deficiency of CRIF1 in 
      podocytes resulted in profound and progressive albuminuria from 3 weeks of age; 
      the CRIF1-deficient mice also developed glomerular and tubulointerstitial lesions 
      by 10 weeks of age. Furthermore, marked glomerular sclerosis and interstitial 
      fibrosis were observed in homozygous CRIF1-deficient mice at 20 weeks of age. In 
      cultured mouse podocytes, loss of CRIF1 resulted in OxPhos dysfunction and marked 
      loss or abnormal aggregation of F-actin. These findings indicate that the OxPhos 
      status determines the integrity of podocytes and their ability to maintain a 
      tight barrier and control albuminuria. Analyses of the glomerular function of the 
      podocyte-specific primary OxPhos dysfunction model mice demonstrate a link 
      between podocyte mitochondrial dysfunction, progressive glomerular sclerosis, and 
      tubulointerstitial diseases.
FAU - Na, Ki Ryang
AU  - Na KR
AD  - Department of Nephrology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
FAU - Jeong, Jin Young
AU  - Jeong JY
AD  - Department of Nephrology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
FAU - Shin, Jin Ah
AU  - Shin JA
AD  - Department of Nephrology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
FAU - Chang, Yoon-Kyung
AU  - Chang YK
AD  - Department of Nephrology, Daejeon St. Mary's Hospital, Catholic University of 
      Korea, Daejeon 34572, Korea.
FAU - Suh, Kwang-Sun
AU  - Suh KS
AUID- ORCID: 0000-0003-3874-864X
AD  - Department of Pathology, Chungnam National University School of Medicine, Daejeon 
      35015, Korea.
FAU - Lee, Kang Wook
AU  - Lee KW
AD  - Department of Nephrology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
FAU - Choi, Dae Eun
AU  - Choi DE
AUID- ORCID: 0000-0003-2870-3958
AD  - Department of Nephrology, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon 35015, Korea.
LA  - eng
GR  - 2017R1D1AB03035061/National Research Foundation of Korea/
GR  - to K.W.L./Chungnam National University Hospital Research Fund/
PT  - Journal Article
DEP - 20210502
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Crif1 protein, mouse)
RN  - 0 (Peptides)
SB  - IM
MH  - Albuminuria/genetics/*metabolism/pathology
MH  - Animals
MH  - Cell Cycle Proteins/*deficiency/genetics/*metabolism
MH  - Diabetic Nephropathies/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Fibrosis
MH  - Kidney/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/genetics/*metabolism
MH  - Mitochondrial Membranes/metabolism
MH  - Oxidative Phosphorylation
MH  - Peptides/metabolism
MH  - Podocytes/*metabolism
MH  - Sclerosis/genetics/*metabolism/pathology
PMC - PMC8124436
OTO - NOTNLM
OT  - CRIF1
OT  - albuminuria
OT  - glomerular sclerosis
OT  - mitochondrial oxidative phosphorylation
OT  - podocyte
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/23 06:00
PMCR- 2021/05/02
CRDT- 2021/06/02 01:06
PHST- 2021/04/13 00:00 [received]
PHST- 2021/04/26 00:00 [revised]
PHST- 2021/04/26 00:00 [accepted]
PHST- 2021/06/02 01:06 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/23 06:00 [medline]
PHST- 2021/05/02 00:00 [pmc-release]
AID - ijms22094827 [pii]
AID - ijms-22-04827 [pii]
AID - 10.3390/ijms22094827 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 May 2;22(9):4827. doi: 10.3390/ijms22094827.