A Mitochondrial RNAi Screen Defines Cellular Bioenergetic Determinants and Identifies an Adenylate Kinase as a Key Regulator of ATP Levels

摘要: Summary Altered cellular bioenergetics and mitochondrial function are major features of several diseases, including cancer, diabetes, neurodegenerative disorders. Given this important link to human health, we sought define proteins within mitochondria that critical for maintaining homeostatic ATP levels. We screened an RNAi library targeting >1,000 nuclear-encoded genes whose protein products localize the in multiple metabolic conditions order examine their effects on identified a mechanism by which electron transport chain (ETC) perturbation under glycolytic increased production through enhanced flux, thereby highlighting potential plasticity. Additionally, adenylate kinase (AK4) regulates levels AMPK signaling expression significantly correlates with glioma patient survival. This study maps bioenergetic landscape context varied substrates begins key clinical outcome.