Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

• MeSH
• Biosynthetic Pathways physiology   MeSH
• Energy Metabolism physiology   MeSH
• Stress, Physiological * MeSH
• Gene Knockout Techniques MeSH
• HEK293 Cells MeSH
• S Phase Cell Cycle Checkpoints physiology   MeSH
• Humans MeSH
• RNA, Small Interfering metabolism   MeSH
• Mitochondria metabolism   MeSH
• Mutation MeSH
• Mice, Inbred BALB C MeSH
• Mice, Nude MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Paraganglioma genetics   pathology   MeSH
• Electron Transport Complex II genetics   metabolism   MeSH
• Succinate Dehydrogenase genetics   metabolism   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH