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

Paul Hsu, Xiaolei Liu, Jun Zhang, Hong-Gang Wang, Ji Ming Ye, Yuguang Shi

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)643-652
Number of pages10
JournalAutophagy
Volume11
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Barth Syndrome
Mitochondrial Degradation
Cardiolipins
Oxidative Phosphorylation
Phospholipids
Premature Mortality
Doxycycline
Dilated Cardiomyopathy
Quality Control
Mitochondria
Oxidative Stress
Pharmacology
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Hsu, Paul ; Liu, Xiaolei ; Zhang, Jun ; Wang, Hong-Gang ; Ye, Ji Ming ; Shi, Yuguang. / Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. In: Autophagy. 2015 ; Vol. 11, No. 4. pp. 643-652.
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Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. / Hsu, Paul; Liu, Xiaolei; Zhang, Jun; Wang, Hong-Gang; Ye, Ji Ming; Shi, Yuguang.

In: Autophagy, Vol. 11, No. 4, 01.01.2015, p. 643-652.

Research output: Contribution to journalArticle

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