Prohibitin 2 deficiency impairs cardiac fatty acid oxidation and causes heart failure

Fatty acids are the most major substrate source for adult cardiac energy generation. Prohibitin 2 (PHB2), a highly conserved protein located in mitochondrial inner membrane, plays key roles in cellular energy metabolic homeostasis. However, its functions in regulating cardiac fatty acid metabolism h...

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Bibliographic Details
Published in:Cell death & disease 2020-03, Vol.11 (3), p.181-181, Article 181
Main Authors: Wu, Dechao, Jian, Chongshu, Peng, Qi, Hou, Tingting, Wu, Keling, Shang, Bizhi, Zhao, Minglei, Wang, Yanru, Zheng, Wen, Ma, Qi, Li, Chuan-Yun, Cheng, Heping, Wang, Xianhua, Zhao, Ling
Format: Article
Language:English
Subjects:
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Animals
Antibodies
Biochemistry
Biomedical and Life Sciences
Cardiomyocytes
Carnitine
Cell Biology
Cell Culture
Congestive heart failure
Fatty acids
Fatty Acids - metabolism
Heart failure
Heart Failure - metabolism
Heart rate
Homeostasis
Humans
Immunology
Life Sciences
Metabolic disorders
Metabolism
Mice
Mitochondria
Oxidation
Oxidation-Reduction
Prohibitin
Repressor Proteins - deficiency
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Summary:Fatty acids are the most major substrate source for adult cardiac energy generation. Prohibitin 2 (PHB2), a highly conserved protein located in mitochondrial inner membrane, plays key roles in cellular energy metabolic homeostasis. However, its functions in regulating cardiac fatty acid metabolism have remained largely unknown. Our study demonstrates that cardiac-specific knockout of Phb2 leads to accumulation of lipid droplets and causes heart failure. Mechanistically, ablation of PHB2 impairs cardiac fatty acid oxidation (FAO) through downregulating carnitine palmitoyltransferase1b (CPT1b), a rate-limiting enzyme of cardiac mitochondrial FAO. Moreover, overexpression of CPT1b alleviates impaired FAO in PHB2-deficient cardiomyocytes. Thus, our study provides direct evidence for the link between PHB2 and cardiac fatty acid metabolism. Our study points out that PHB2 is a potential FAO regulator in cardiac mitochondrial inner membrane, as well as the connection between PHB2 and CPT1b and their relationships to cardiac pathology especially to cardiac fatty acid metabolic disorder.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-2374-7