PMID- 34392303
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20240226
IS  - 2041-4889 (Electronic)
VI  - 12
IP  - 8
DP  - 2021 Aug 14
TI  - CPT1alpha maintains phenotype of tubules via mitochondrial respiration during kidney 
      injury and repair.
PG  - 792
LID - 10.1038/s41419-021-04085-w [doi]
LID - 792
AB  - Impaired energy metabolism in proximal tubular epithelial cells (PTECs) is 
      strongly associated with various kidney diseases. Here, we characterized proximal 
      tubular phenotype alternations during kidney injury and repair in a mouse model 
      of folic acid nephropathy, in parallel, identified carnitine palmitoyltransferase 
      1alpha (CPT1alpha) as an energy stress response accompanied by renal tubular 
      dedifferentiation. Genetic ablation of Cpt1alpha aggravated the tubular injury and 
      interstitial fibrosis and hampered kidney repair indicate that CPT1alpha is vital for 
      the preservation and recovery of tubular phenotype. Our data showed that the 
      lipid accumulation and mitochondrial mass reduction induced by folic acid were 
      persistent and became progressively more severe in PTECs without CPT1alpha. 
      Interference of CPT1alpha reduced capacities of mitochondrial respiration and ATP 
      production in PTECs, and further sensitized cells to folic acid-induced 
      phenotypic changes. On the contrary, overexpression of CPT1alpha protected 
      mitochondrial respiration and prevented against folic acid-induced tubular cell 
      damage. These findings link CPT1alpha to intrinsic mechanisms regulating the 
      mitochondrial respiration and phenotype of kidney tubules that may contribute to 
      renal pathology during injury and repair.
CI  - (c) 2021. The Author(s).
FAU - Yuan, Qi
AU  - Yuan Q
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
AD  - Department of Nephrology, The Affiliated Suzhou Hospital of Nanjing Medical 
      University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 
      Suzhou, China.
FAU - Lv, Yunhui
AU  - Lv Y
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Ding, Hao
AU  - Ding H
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Ke, Qingqing
AU  - Ke Q
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Shi, Caifeng
AU  - Shi C
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Luo, Jing
AU  - Luo J
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Jiang, Lei
AU  - Jiang L
AUID- ORCID: 0000-0002-7322-4502
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China. jianglei@njmu.edu.cn.
FAU - Yang, Junwei
AU  - Yang J
AUID- ORCID: 0000-0001-9008-5826
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China. jwyang@njmu.edu.cn.
FAU - Zhou, Yang
AU  - Zhou Y
AUID- ORCID: 0000-0003-0453-4598
AD  - Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China. zhouyang@njmu.edu.cn.
LA  - eng
GR  - 81873618/National Natural Science Foundation of China (National Science 
      Foundation of China)/
GR  - BK20201497/Natural Science Foundation of Jiangsu Province (Jiangsu Provincial 
      Natural Science Foundation)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210814
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 935E97BOY8 (Folic Acid)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
SB  - IM
MH  - Adenosine Triphosphate/biosynthesis
MH  - Animals
MH  - Blood Urea Nitrogen
MH  - Carnitine O-Palmitoyltransferase/deficiency/*metabolism
MH  - Cell Respiration
MH  - Cells, Cultured
MH  - Creatinine/metabolism
MH  - Fibrosis
MH  - Folic Acid
MH  - Kidney Diseases/enzymology/pathology
MH  - Kidney Tubules/*enzymology/injuries/*pathology/ultrastructure
MH  - Lipid Metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*metabolism/ultrastructure
MH  - Phenotype
MH  - Mice
PMC - PMC8364553
COIS- The authors declare no competing interests.
EDAT- 2021/08/16 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/08/14
CRDT- 2021/08/15 20:58
PHST- 2021/05/22 00:00 [received]
PHST- 2021/08/06 00:00 [accepted]
PHST- 2021/07/29 00:00 [revised]
PHST- 2021/08/15 20:58 [entrez]
PHST- 2021/08/16 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/08/14 00:00 [pmc-release]
AID - 10.1038/s41419-021-04085-w [pii]
AID - 4085 [pii]
AID - 10.1038/s41419-021-04085-w [doi]
PST - epublish
SO  - Cell Death Dis. 2021 Aug 14;12(8):792. doi: 10.1038/s41419-021-04085-w.