Scholarlink

<p>Lipid droplet (LD) -mitochondrion contacts play a crucial role in regulating energy metabolism and fatty acid oxidation in skeletal muscle cells. However, the proteins that regulate these interactions remain poorly understood. Here, we demonstrate that the binding between ADP-ribosylation factor 1(ARF1) and perilipin2 (Plin2) regulates LD-mitochondrion contacts under starvation conditions, facilitating the transfer of fatty acids from LDs to mitochondria. In C2C12 cells, starvation increased ARF1’s GTP-binding activity and its localization to mitochondria, enhancing ARF1’s binding to Plin2 and facilitating fatty acid flow from LDs to mitochondria. In contrast, knockdown of ARF1 reduced LD-mitochondrion interactions and blocked fatty acids transfer. Additionally, ARF1-mediated interactions were regulated by AMPK; inhibiting AMPK activity reduced ARF1 localization to LDs and mitochondria, and blocked LD-mitochondrion interactions. In mice, starvation increased ARF1 expression in muscle tissue and LD-mitochondrion contacts. Conversely, inhibiting ARF1 led to lipid accumulation in muscle tissue. In conclusion, our work suggests that ARF1 is a critical regulator of LD-mitochondrion interactions and plays a significant role in energy metabolism regulation in skeletal muscle.</p><p></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

AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月18日

查看全文
  • Lupeng Chen,
  • Yue Liu,
  • Junzhi Zhang,
  • Tongxing Song,
  • Jian Wu,
  • Zhuqing Ren

摘要

Lipid droplet (LD) -mitochondrion contacts play a crucial role in regulating energy metabolism and fatty acid oxidation in skeletal muscle cells. However, the proteins that regulate these interactions remain poorly understood. Here, we demonstrate that the binding between ADP-ribosylation factor 1(ARF1) and perilipin2 (Plin2) regulates LD-mitochondrion contacts under starvation conditions, facilitating the transfer of fatty acids from LDs to mitochondria. In C2C12 cells, starvation increased ARF1’s GTP-binding activity and its localization to mitochondria, enhancing ARF1’s binding to Plin2 and facilitating fatty acid flow from LDs to mitochondria. In contrast, knockdown of ARF1 reduced LD-mitochondrion interactions and blocked fatty acids transfer. Additionally, ARF1-mediated interactions were regulated by AMPK; inhibiting AMPK activity reduced ARF1 localization to LDs and mitochondria, and blocked LD-mitochondrion interactions. In mice, starvation increased ARF1 expression in muscle tissue and LD-mitochondrion contacts. Conversely, inhibiting ARF1 led to lipid accumulation in muscle tissue. In conclusion, our work suggests that ARF1 is a critical regulator of LD-mitochondrion interactions and plays a significant role in energy metabolism regulation in skeletal muscle.