Altered mitochondrial dynamics and response to insulin in cybrid cells harboring a diabetes-susceptible mitochondrial DNA haplogroup

Hsiao Mei Kuo, Shao Wen Weng, Alice Y.W. Chang, Hung Tu Huang, Hung Yu Lin, Jiin Haur Chuang, Tsu Kung Lin, Chia Wei Liou, Ming Hong Tai, Ching Yi Lin, Pei Wen Wang

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

The advantage of using a cytoplasmic hybrid (cybrid) model to study the genetic effects of mitochondria is that the cells have the same nuclear genomic background. We previously demonstrated the independent role of mitochondria in the pathogenesis of insulin resistance (IR) and pro-inflammation in type 2 diabetes. In this study, we compared mitochondrial dynamics and related physiological functions between cybrid cells harboring diabetes-susceptible (B4) and diabetes-protective (D4) mitochondrial haplogroups, especially the responses before and after insulin stimulation. Cybrid B4 showed a more fragmented mitochondrial network, impaired mitochondrial biogenesis and bioenergetics, increased apoptosis and ineffective mitophagy and a low expression of fusion-related molecules. Upon insulin stimulation, increases in network formation, mitochondrial DNA (mtDNA) content, and ATP production were observed only in cybrid D4. Insulin promoted a pro-fusion dynamic status in both cybrids, but the trend was greater in cybrid D4. In cybrid B4, the imbalance of mitochondrial dynamics and impaired biogenesis and bioenergetics, and increased apoptosis were significantly improved in response to antioxidant treatment. We concluded that diabetes-susceptible mtDNA variants are themselves resistant to insulin.

原文English
頁(從 - 到)116-129
頁數14
期刊Free Radical Biology and Medicine
96
DOIs
出版狀態Published - 2016 七月 1

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 生理學(醫學)

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