Mief1 augments thyroid cell dysfunction and apoptosis through inhibiting AMPK-PTEN signaling pathway

Abstract

Objective: Inflammation-mediated thyroid cell dysfunction and apoptosis increases the like-hood of hypothyroidism.

Aim: Our aim in the present study is to explore the role of mitochondrial elongation factor 1 (Mief1) in thyroid cell dysfunction induced by TNFα.

Materials and methods: Different doses of TNFα were used to incubate with thyroid cells in vitro. The survival rate, apoptotic index and proliferation capacity of thyroid cells were measured. Cellular energy metabolism and endoplasmic reticulum function related to protein synthesis were detected.

Results: In response to TNFα treatment, the levels of Mief1 were increased, coinciding with a drop in the viability of thyroid cells in vitro. Loss of Mief1 attenuates TNFα-induced cell death through reducing the ratio of cell apoptosis. Further, we found that Mief1 deletion reversed cell energy metabolism and this effect was attributable to mitochondrial protection. Mief1 knockdown sustained mitochondrial membrane potential and reduced mitochondrial ROS overproduction. In addition, Mief1 knockdown also reduced endoplasmic reticulum stress, as evidenced by decreased levels of Chop and Caspase-12. Finally, our data verified that TNFα treatment inhibited the activity of AMPK-PTEN pathway whereas Mief1 deletion reversed the activity of AMPK and thus promoted the upregulation of PTEN. However, inhibition of AMPK-PTEN pathways could abolish the beneficial effects exerted by Mief1 deletion on thyroid cells damage and dysfunction.

Conclusions: Altogether, our data indicate that immune abnormality-mediated thyroid cell dysfunction and death are alleviated by Mief1 deletion possible driven through reversing the activity of AMPK-PTEN pathways.

Keywords:

• Thyroid cell death
• Mief1
• AMPK
• PTEN

Disclosure statement

The authors have declared that they have no conflicts of interest.

Data availability

All data generated or analyzed during this study are included in this published article.