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Deletion of Cyclophilin D Impairs β-Oxidation and Promotes Glucose Metabolism

Tavecchio, Michele LU ; Lisanti, Sofia; Bennett, Michael J; Languino, Lucia R and Altieri, Dario C (2015) In Scientific Reports 5.
Abstract

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore,... (More)

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo.

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published
keywords
Adenosine Triphosphate, Animals, Blood Glucose, Carbohydrate Metabolism, Cells, Cultured, Cholesterol, Citric Acid Cycle, Cyclophilins, Diet, High-Fat, Female, Glucose Tolerance Test, Glycolysis, Immunohistochemistry, Insulin, Insulin-Secreting Cells, Lipid Peroxidation, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Pancreas, Triglycerides, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.
in
Scientific Reports
volume
5
publisher
Nature Publishing Group
external identifiers
  • scopus:84946146043
ISSN
2045-2322
DOI
10.1038/srep15981
language
English
LU publication?
no
id
c4a71e22-e365-4384-be30-59a3160b2081
date added to LUP
2017-03-07 09:04:36
date last changed
2017-09-24 05:08:24
@article{c4a71e22-e365-4384-be30-59a3160b2081,
  abstract     = {<p>Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo.</p>},
  articleno    = {15981},
  author       = {Tavecchio, Michele and Lisanti, Sofia and Bennett, Michael J and Languino, Lucia R and Altieri, Dario C},
  issn         = {2045-2322},
  keyword      = {Adenosine Triphosphate,Animals,Blood Glucose,Carbohydrate Metabolism,Cells, Cultured,Cholesterol,Citric Acid Cycle,Cyclophilins,Diet, High-Fat,Female,Glucose Tolerance Test,Glycolysis,Immunohistochemistry,Insulin,Insulin-Secreting Cells,Lipid Peroxidation,Liver,Male,Mice,Mice, Inbred C57BL,Mice, Knockout,Mitochondria,Pancreas,Triglycerides,Journal Article,Research Support, N.I.H., Extramural,Research Support, U.S. Gov't, Non-P.H.S.},
  language     = {eng},
  month        = {10},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Deletion of Cyclophilin D Impairs β-Oxidation and Promotes Glucose Metabolism},
  url          = {http://dx.doi.org/10.1038/srep15981},
  volume       = {5},
  year         = {2015},
}