Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy

Hsu, P, Liu, X, Zhang, J, Wang, H, Ye, J and Shi, Y 2015, 'Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy', Autophagy, vol. 11, no. 4, pp. 643-652.


Document type: Journal Article
Collection: Journal Articles

Title Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy
Author(s) Hsu, P
Liu, X
Zhang, J
Wang, H
Ye, J
Shi, Y
Year 2015
Journal name Autophagy
Volume number 11
Issue number 4
Start page 643
End page 652
Total pages 10
Publisher Landes Bioscience
Abstract Tafazzin (TAZ) is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mutations of TAZ cause Barth syndrome, which is characterized by mitochondrial dysfunction and dilated cardiomyopathy, leading to premature death. However, the molecular mechanisms underlying the cause of mitochondrial dysfunction in Barth syndrome remain poorly understood. Here we investigated the role of TAZ in regulating mitochondrial function and mitophagy. Using primary mouse embryonic fibroblasts (MEFs) with doxycycline-inducible knockdown of Taz, we showed that TAZ deficiency in MEFs caused defective mitophagosome biogenesis, but not other autophagic processes. Consistent with a key role of mitophagy in mitochondria quality control, TAZ deficiency in MEFs also led to impaired oxidative phosphorylation and severe oxidative stress. Together, these findings provide key insights on mitochondrial dysfunction in Barth syndrome, suggesting that pharmacological restoration of mitophagy may provide a novel treatment for this lethal condition.
Subject Metabolic Medicine
Basic Pharmacology
Keyword(s) autophagy
Barth syndrome
cardiolipin
mitochondrial dysfunction
mitophagosome
mitophagy
tafazzin
DOI - identifier 10.1080/15548627.2015.1023984
Copyright notice © 2015 Taylor & Francis Group, LLC
ISSN 1554-8627
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