Core Insights - The research conducted by Fudan University reveals a novel role of Acetyl-CoA as a "metabolic messenger" that directly regulates mitochondrial autophagy, providing a new therapeutic target for overcoming resistance to KRAS inhibitors in pancreatic cancer [1][7]. Group 1: Research Findings - The study highlights that during nutrient scarcity, Acetyl-CoA bypasses the well-known AMPK and mTOR pathways, directly signaling to mitochondria through the protein NLRX1 [1][2]. - The research team utilized CRISPR/Cas9 technology to identify NLRX1 as a key protein involved in this newly discovered signaling pathway [3][4]. - The interaction between Acetyl-CoA and NLRX1 was confirmed through a "molecular fishing" experiment, demonstrating a direct binding relationship [4][5]. Group 2: Implications for Cancer Treatment - The findings indicate that in nutrient-rich conditions, high levels of Acetyl-CoA inhibit mitochondrial autophagy by locking NLRX1 in a dormant state, while nutrient deprivation releases this inhibition, promoting autophagy [6][7]. - The study also uncovers a mechanism by which cancer cells develop resistance to KRAS inhibitors by activating mitochondrial autophagy in response to decreased Acetyl-CoA levels, suggesting a potential new treatment strategy [7][8]. - Targeting the Acetyl-CoA-NLRX1 axis could enhance the effectiveness of KRAS inhibitors, offering new hope for cancer patients facing treatment resistance [7][8].