Work

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

Year: 2015

Type: article

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.

Source: Autophagy

DOI: 10.1080/15548627.2015.1023984

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

Institutions: Pennsylvania State University, RMIT University

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Barth Syndrome Foundation, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases