Work

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

Year: 2015

Type: article

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, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo.

Source: Scientific Reports

DOI: 10.1038/srep15981

Authors: Michele Tavecchio, Sofia Lisanti, Michael J. Bennett, Lucia R. Languino, Dario C. Altieri

Institutions: The Wistar Institute, Children's Hospital of Philadelphia, University of Pennsylvania, Thomas Jefferson University, Sidney Kimmel Cancer Center

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690