MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signaling in cancer

Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signaling. Here, we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppress the metabolic switch and dampens the viability of transformed cells indicating Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence to: Marcelo G. Bonini, Ph.D., Departments of Medicine, Pathology and Pharmacology, University of Illinois at Chicago, UIC, 909 S. Wolcott Ave, COMRB 1131, Chicago, IL, 60612, Phone – (312) 355-5948, [email protected]. *These authors contributed equally to this work Authors contributions: Key experiments were performed by PCH, KAF, MM, ALA, DNK, DG. PCH, KAF, MM, ALA, DNK, AMD, JHS, MGB conceived and designed experiments. Data interpretation and hypothesis were generated by PCH, KAF, MM, AMD, AKB, RDM, MELC, JHS, MGB. DNK, AKB, AMD provided exclusive reagents and model systems. AKB built, classified and analyzed data from TMA. AMD, RDM, JHS, MELC and MGB – wrote the manuscript. MGB had the general oversight of the project. Competing Financial Interests: None to disclose HHS Public Access Author manuscript Nat Commun. Author manuscript; available in PMC 2015 August 05. Published in final edited form as: Nat Commun. ; 6: 6053. doi:10.1038/ncomms7053. A uhor M anscript