Scholarlink

<p>Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder characterized by excessive fat accumulation in the liver. Aberrant enrichment of mitochondria-associated membranes (MAMs) plays a significant role in promoting the overproduction of reactive oxygen species (ROS). However, the precise role of MAMs in NAFLD and the potential targets regulating MAMs formation remain unclear.This study demonstrated that SIRT1 inhibits abnormal MAM enrichment in the livers of NAFLD mice and PA-incubated hepatocytes. Moreover, the protective effects of SIRT1 against NAFLD caused by excessive caloric intake are closely associated with its ability to block MAMs-induced mitochondrial Ca<sup>2</sup>⁺ overload. This regulation alleviates Ca<sup>2</sup>⁺ dysregulation and subsequently inhibits ROS overproduction-mediated mitochondrial dysfunction. Transcriptomic analysis confirmed that mouse double minute 2 homolog (MDM2) may acts as a downstream target of activated SIRT1 in regulating MAMs formation and thereby protecting against the development of NAFLD. Taken together, this reseach revealed that SIRT1 activation inhibits the aberrant formation of MAMs caused by excessive calorie intake. This effect is linked to the suppression of MDM2 expression and disruption of its interaction of MDM2 with resident MAMs Ca2 + channels by SIRT1, ultimately alleviating mitochondrial Ca<sup>2</sup>⁺ overload induced mitochondria oxidative stress.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Regulatory role of sirtuin-1 by targeting MDM2 to mitochondria-associated membranes formation in the treatment of NAFLD

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月28日

查看全文
  • Rui Zhang,
  • Quanwei Zhang,
  • ZiYi Cui,
  • BenZeng Huang,
  • Manman Li,
  • Haitian Ma

摘要

Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder characterized by excessive fat accumulation in the liver. Aberrant enrichment of mitochondria-associated membranes (MAMs) plays a significant role in promoting the overproduction of reactive oxygen species (ROS). However, the precise role of MAMs in NAFLD and the potential targets regulating MAMs formation remain unclear.This study demonstrated that SIRT1 inhibits abnormal MAM enrichment in the livers of NAFLD mice and PA-incubated hepatocytes. Moreover, the protective effects of SIRT1 against NAFLD caused by excessive caloric intake are closely associated with its ability to block MAMs-induced mitochondrial Ca2⁺ overload. This regulation alleviates Ca2⁺ dysregulation and subsequently inhibits ROS overproduction-mediated mitochondrial dysfunction. Transcriptomic analysis confirmed that mouse double minute 2 homolog (MDM2) may acts as a downstream target of activated SIRT1 in regulating MAMs formation and thereby protecting against the development of NAFLD. Taken together, this reseach revealed that SIRT1 activation inhibits the aberrant formation of MAMs caused by excessive calorie intake. This effect is linked to the suppression of MDM2 expression and disruption of its interaction of MDM2 with resident MAMs Ca2 + channels by SIRT1, ultimately alleviating mitochondrial Ca2⁺ overload induced mitochondria oxidative stress.