Core Insights - Recent research indicates that autophagy is activated during exercise, mediating the health benefits associated with physical activity. However, the molecular mechanisms regulating skeletal muscle autophagy during exercise remain unclear [3][5]. Group 1: Research Findings - A study published in Cell Chemical Biology reveals that lactate produced during exercise enhances autophagy in skeletal muscle by lactylation of the mTOR protein [3][5]. - Lactate is identified as a positive regulator of autophagy in muscle cells, with levels rapidly increasing after a single exercise session [5]. - The study demonstrates that lactate promotes lactylation at the K921 site of the mTOR protein, inhibiting mTORC1 activity and enhancing autophagy [5][8]. Group 2: Implications - This research fundamentally redefines lactate, transforming it from a mere metabolic byproduct into a key signaling molecule that mediates exercise-induced skeletal muscle adaptation [7][8]. - The findings provide a conceptual framework for understanding how muscle metabolism translates into adaptive responses, opening new avenues for the treatment of muscle and metabolic diseases [8].

Core Insights - Lung cancer is a leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases, and lung adenocarcinoma (LUAD) being the most common subtype. The five-year survival rate for lung adenocarcinoma patients is below 26% [2] - The study published in Cell Discovery reveals that ferroptosis-induced SUMO2 lactylation counteracts ferroptosis by enhancing the degradation of ACSL4 in lung adenocarcinoma, identifying a key regulatory factor in the resistance to ferroptosis and proposing a new strategy for cancer treatment based on ferroptosis [3][8] Group 1: Ferroptosis and Cancer Treatment - Ferroptosis is a regulated form of cell death characterized by the accumulation of reactive oxygen species (ROS), lipid peroxides, and increased levels of divalent iron (Fe2+), showing significant effectiveness in overcoming resistance to traditional cancer therapies [5] - The study indicates that ferroptosis significantly increases lactate accumulation and subsequent protein lactylation, which contributes to the resistance of lung adenocarcinoma cells to ferroptosis [6] Group 2: Key Findings of the Research - SUMO2-K11 lactylation is identified as a critical factor determining the resistance to ferroptosis in lung adenocarcinoma, as it weakens the interaction between SUMO2 and ACSL4, promoting ACSL4 degradation and disrupting lipid metabolism [6][8] - AARS1 is recognized as the lactylation transferase for SUMO2-K11la, while HDAC1 acts as the de-lactylase. The research team developed a cell-penetrating peptide that specifically inhibits SUMO2-K11la, enhancing ferroptosis and increasing the sensitivity of lung adenocarcinoma to the chemotherapy drug cisplatin [6][8]