Thioredoxin-1 maintains mitochondrial function via mechanistic target of rapamycin signalling in the heart.

ABSTRACT:

Aims

Thioredoxin 1 (Trx1) is an evolutionarily conserved oxidoreductase that cleaves disulphide bonds in oxidized substrate proteins such as mechanistic target of rapamycin (mTOR) and maintains nuclear-encoded mitochondrial gene expression. The cardioprotective effect of Trx1 has been demonstrated via cardiac-specific overexpression of Trx1 and dominant negative Trx1. However, the pathophysiological role of endogenous Trx1 has not been defined with a loss-of-function model. To address this, we have generated cardiac-specific Trx1 knockout (Trx1cKO) mice.

Methods and results

Trx1cKO mice were viable but died with a median survival age of 25.5 days. They developed heart failure, evidenced by contractile dysfunction, hypertrophy, and increased fibrosis and apoptotic cell death.

SUBMITTER: Oka SI 

PROVIDER: S-EPMC7825501 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature