2025/12/11 by Bruna Martins Garcia, Patricia Altea‐Manzano · 1 voice
Biochemistry, Genetics and Molecular Biology · #Cancer, Hypoxia, and Metabolism #ATP Synthase and ATPases Research #Mitochondrial Function and Pathology
paper · doi:10.1158/0008-5472.can-25-5633
openalex publication_date 2025/12/11 · openalex created_date 2025/12/11 · openalex updated_date 2026/07/25
The tumor microenvironment imposes diverse metabolic challenges to cancer cells. Overcoming these challenges is essential for survival, proliferation, and dissemination. However, how cancer cells cope with the harsh environment and how the different coexisting stresses affect the tumor in vivo are unknown. Recently, Groessl and colleagues published their findings in Science showing that acidosis outweighs all other stresses and plays a major role in adaptation to them. Mechanistically, acidosis inhibits the ERK-dynamin-related protein 1 (DRP1) pathway, resulting in mitochondria elongation, which triggers a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS). These findings highlight the plasticity of cancer cell mitochondria and refute the previous belief that cancer mitochondria are inherently dysfunctional. Indeed, inhibition of mitochondrial fusion or OXPHOS in acidic tumors is sufficient to promote cell death. Thus, enhancing respiration under acidosis comes to light as an essential metabolic adaptation to cancer survival and proliferation, and targeting how cancer cells adapt to acidosis emerges as a new avenue for therapy.