The mitochondrial thioredoxin is required for liver development in zebrafish.

Thioredoxins (Trxs) are a class of small molecular redox proteins that play an important role in scavenging abnormally accumulated reactive oxygen species (ROS). Thioredoxin 2 (Trx2) is one member of this family located in mitochondria. Trx2 protects cells from increased oxidative stress and has anti-apoptosis function. Knockout of Trx2 in mice led to early embryonic lethality. However, the essential role of Trx2 during embryogenesis remains unclear. To further investigate the role of Trx2 during embryonic development, we performed Trx2 knockdown in zebrafish and investigated the regulation role of Trx2 during embryonic development. Our results indicate that Trx2 had a high expression in early zebrafish embryos and its knockdown in zebrafish led to defective liver development mainly due to increased hepatic cell death. The increased ROS and the imbalance of members of the Bcl-2 family were involved in cell death induced by Trx2 suppression in zebrafish. The dysregulation of Bax, puma and Bcl-xl promoted the reduction of mitochondrial trans-membrane potential and the mitochondria membrane permeabilization (MMP), which initiated the mitochondrial apoptosis pathway. Additionally, we found that the increase of relocated GAPDH in mitochondria may be another factor responsible for the mitochondrial catastrophe.

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